bluuebunny/crossref_metadata_2025 huggingface dataset:
Executive functions as early cognitive markers and predictors of people with high risk to develop Alzheimer’s Clinical Syndrome
Authors: Guinea Sara Fernández , Fernández Almudena Junquera , Olazarán Javier , Marqués Javier González , Parra‐Rodriguez Mario A
Published: June 2023

Background

Recent research has pointed to impaired executive functions (EF) as a potential early predictor of progression from Mild Cognitive Impairment (MCI) to dementia in the Alzheimer’s clinical syndrome (ACS) (Junquera et al, 2020). In this study, we investigated the EF tests that hold the best sensitivity and specificity to discriminate, using baseline data, between cognitively unimpaired older adults and MCI patients who converted to ACS or remained stable after two years (aim 1). We then explored which EF components can best predict conversion from MCI to ACS in a two‐year follow‐up (aim 2).

Method

We assessed 210 participants, 71 cognitively unimpaired older adults (CU) and 130 MCI patients. Eight tests assessing EF (Similarities, Arithmetic, Reverse Digits, and Letters and Numbers, Trail‐Making Test, Stroop Test, Verbal Fluency – phonemic and categories, and Zoo Map) were administered at baseline and at 2‐year follow‐up, together with cognitive screening tools and IADL measures. ROC analysis was used to address aim 1. A binary regression model was then used to examine the EF components and tests identified via aim 1 that reliably predict progression from MCI to ACS (aim 2).

Result

Baseline scores from the TMT and semantic categories' fluency were significantly lower in MCI patients who later progressed to ACS (p<.001) than those who remained stable. ROC analysis showed that the TMT and semantic category fluency test were the best tests to differentiate at baseline between MCI converter and non‐converter (AUC = 0.768 and 0.77, respectively), CU and MCI converter (AUC = 0.864 and 0.876, respectively), and between CU and MCI no converter (AUC = 0.602 and 0.673, respectively). Binary logistic regression results revealed that indeed, the TMT and semantic categories fluency test significantly predicted the conversion from MCI to ACS (p<.05).

Conclusion

Switching abilities and verbal fluency (categories) were the executive function that best predicts MCI to ACS conversion in two years. TMT and semantic verbal fluency clearly identify people with high risk to develop ACS in two years. It is recommended to include these tests in the prodromal Alzheimer’s disease characterization.
Application of advanced language technologies in analysis of category naming fluency task in healthy participants
Authors: Gonzalez‐Recober Carmen , Cho Sunghye , Liberman Mark Y , Grossman Murray , Nevler Naomi
Published: June 2023

Background

Category naming fluency tasks have been used frequently to measure patients’ working memory and executive functions. Previous studies show that differences in scores in this task could reflect features of neurodegenerative disease. To better understand decreased performance in patients, it is critical to establish performance in healthy aging populations. Here, we investigated differences in total scores and lexical/speech features of words produced during animal fluency tasks of healthy young and older speakers which can only be derived with novel, automated, computational technologies.

Method

Data were collected in 52 young participants (26.9% males, mean age = 23.5±3.17) and 46 elderly participants (63.0% males, mean age = 69.9±6.77). Participants were instructed to list as many animals as possible for 60 seconds. Speech was transcribed and automatically force‐aligned. Transcripts were run through our automated Python pipeline to calculate the total number of animals listed and rate each word for the following semantic parameters: age of acquisition (AoA), ambiguity, familiarity, frequency. We also calculated phonetic and semantic distances between each word and its antecedent. Linear regression models tested the association between these automated language measures and total scores. We also examined the differences of the young and elderly groups using t‐tests.

Result

Elderly participants produced significantly fewer animals than young participants (p<0.001). Higher overall scores were associated with higher mean AoA (beta = 0.22, p = 0.049) and longer word duration (beta = 1.62, p = 0.037), as well as less frequent (beta = ‐0.51, p = 0.021) and familiar (beta = ‐3.96, p<0.001) animal names. We found no interaction with the age groups in any of the models. Elderly participants produced less frequent animal names than young participants (p = 0.029), along with significantly reduced phonetic distance scores (p = 0.008). Elderly participants scored significantly higher articulation rates (p = 0.007) and had a faster speech rate (p<0.001), attributable to producing more non‐animal words.

Conclusion

This study demonstrates the applicability of advanced language technologies in analyzing category naming fluency tasks in healthy adults. We developed an automated scoring system and identify novel semantic and phonetic measures from digitally recorded fluency tasks. We also quantified some confounding age effects which could be explained by lexical/speech differences of words produced by the groups.
Indigenous inclusion in the Canadian therapeutic platform trial for multidomain interventions to prevent dementia
Authors: Furlano Joyla , Walker Jennifer D
Published: June 2023

Background

The Canadian Therapeutic Platform Trial for Multidomain Interventions to Prevent Dementia (CTU) is Canada’s largest national dementia research initiative, evaluating the effectiveness of a web‐based multimodal program in reducing dementia risk among older adults. To date, CTU has not included Indigenous perspectives, culture, or context in the development of the intervention or study design, and therefore does not reflect the priorities and needs of Indigenous communities.

Method

In consultation with Indigenous community partners, a content analysis of CTU methodologies is currently underway to identify areas for improved cultural relevancy within the program’s modules.

Result

Based on findings from the content analysis, an Indigenous adaptation of the program will be developed and piloted in Indigenous communities in Canada. General suggestions on how to improve CTU from a cultural perspective will also be provided to inform future CTU trials.

Conclusion

This community‐driven research will help shape current and future dementia prevention trials and ensure cultural relevancy in the development of community‐based preventative strategies. Further, it will help ensure that culturally safe and trauma‐informed dementia prevention tools are available to Indigenous peoples in Canada.
Associations between distinct trajectories of body mass index (BMI) over 15 years preceding dementia and incidence of dementia
Authors: Ren Dianxu , Lopez Oscar L. , Lingler Jennifer H , Conley Yvette
Published: June 2023

Background

BMI has been reported to associate with dementia, with both increased and decreased risks. The purpose of this study was to examine longitudinal distinct trajectories of BMI over 15 years preceding dementia with incident dementia using the large national dataset from National Alzheimer’s Coordinating Center (NACC).

Method

We used NACC dataset from 2005 to December 2020 and performed a nested case‐control study (up to 1 to 4 match). The sample included 699 cases of all‐causes dementia with at least 5–years follow‐up time preceding dementia diagnosis, and 2120 non‐dementia controls matched on age, sex, race, education and baseline cognitive status. A group‐based trajectory model was applied to identify longitudinal distinct trajectory groups of BMI among this sample. Conditional logistic regression model was used to evaluate the effect of distinct trajectories of BMI, APOE genotype and the interaction between them with incident dementia.

Result

For the case group (n = 699), mean age at enrollment was 75.5 years and average education in years was 16.1, participants were more female (58.8%), non‐Hispanic white (86.8%) and healthy cognitive status at initial visit (64%). A three‐group linear trajectory model best fit BMI trajectory before the onset of dementia that featured a normal weight‐decreasing BMI group (45.5%), overweight‐decreasing BMI group (43.6%) and obese‐decreasing BMI group (10.9%). There is statistically significant linear decreasing trend over 15 years for each trajectory group (P<0.0001). The average BMI at 15 years preceding dementia for each trajectory group was 22.7, 29.9 and 36.7 respectively. Conditional logistic regression model revealed significant interaction between BMI trajectory group and APOE genotype. Comparing to obese‐decreasing and ε4 non‐carriers, the ε4 carriers in either overweight‐decreasing group or obese‐decreasing group were more likely to develop dementia [OR = 1.53, 95% CI (1.00‐2.34), P = 0.05; OR = 1.88, 95% CI (1.06‐3.34), P = 0.03]. Especially, the ε4 carriers within normal weight‐decreasing BMI group had triple the likelihood of dementia ([OR = 3.25, 95% CI (2.13‐4.94), P<0.0001].

Conclusion

Our findings suggest the existence of distinct developmental trajectories of BMI preceding incident dementia and the possible effect of gene‐environment interaction on dementia. The ε4 carriers within normal weight‐decreasing BMI trajectory group exhibited the highest risk of dementia.
Elevated levels of mosaic aneuploidy in brain cells and fibroblast cell lines from human Huntington’s disease donors and in brain cells from Huntington’s disease mouse models
Authors: Elos Mihret , Caneus Julbert , Ahmed Md. Mahiuddin , Grissom Paula M. , Markham Neil , Johnson Noah R , Chial Heidi J , Potter Huntington
Published: June 2023

Background

Huntington’s disease (HD) is a progressive neurodegenerative disorder that presents with motor and cognitive deficits and psychiatric disturbances. HD is associated with autosomal dominant inheritance of a CAG trinucleotide repeat expansion mutation in the huntingtin (HTT) gene. The huntingtin protein localizes to spindle poles and is required for proper mitotic spindle orientation, chromosome segregation, and cell cycle regulation. The mature mutant huntingtin protein has an expanded polyglutamine region (>35 repeats) near its N terminus, which leads to neuronal dysfunction and death. Mouse models of HD exhibit defects in microtubule function and cell cycle regulation. Studies from our laboratory and others have shown elevated levels of aneuploidy in many neurodegenerative disorders characterized by cognitive deficits, including Alzheimer’s disease and frontotemporal lobar degeneration. Here, we investigated whether chromosome segregation defects that lead to mosaic aneuploidy and consequent apoptosis may also contribute to neuronal loss in HD.

Methods

Single‐cell suspensions from cortex and cerebellum from human HD donors were analyzed using FISH for chromosome 21, NeuN immunostaining, and/or TUNEL staining. Fibroblast cell lines from human HD donors were also analyzed using FISH. Single‐cell suspensions from cortex and cerebellum from HD mouse models were analyzed using FISH for chromosomes 5 and 16. Cell cycle arrest, mitotic spindle defects, ploidy, and apoptosis profiles in the HD fibroblast cell lines are being analyzed by flow cytometry and immunofluorescence microscopy.

Results

Increased levels of mosaic aneuploidy and apoptosis were observed in brain cells and in fibroblast cell lines from HD donors compared to age‐matched healthy control donors. Increased levels of mosaic aneuploidy were also observed in brain cells from HD mice compared to age‐matched wild‐type control mice. Results of ongoing studies of cell cycle and mitotic defects will also be presented.

Conclusions

Taken together with the results of our previous studies, these data provide evidence that chromosome segregation defects that lead to genomic instability may serve as a shared mechanism underlying many neurodegenerative disorders. Our findings highlight the need to further investigate the biological mechanism(s) that contribute to HD pathology and set the stage for novel therapeutic approaches to HD that may also be applied to other neurodegenerative disorders.
Higher plasma proinflammatory cytokines and reduced microglial TREM2 signaling in Late‐life Major Depression
Authors: Pomara Nunzio , Plaska Chelsea Reichert , Bruno Davide , Cejudo Jaime Ramos , Osorio Ricardo S , Pillai Anilkumar , Heslegrave Amanda , Zetterberg Henrik , Blennow Kaj
Published: June 2023

Background

Elevated circulating cytokines leading to microglia activation have been implicated in the increased risk for Alzheimer’s Disease (AD) in depression. However, correlations between peripheral and central inflammatory markers have been inconclusive. Additionally, only some depressives show evidence of increased inflammation.

Microglia can assume anti‐inflammatory states via increased signaling of their TREM2 receptor with potential protective effects against AD including increased phagocytosis and NFkB inflammatory pathway inhibition. This process generates a soluble cleavage product, sTREM2, detected in CSF. Importantly in longitudinal human studies, higher CSF sTREM2 is associated with less brain amyloid deposition, less cognitive decline, and fewer degenerative changes.

These considerations prompted us to determine if higher levels of plasma proinflammatory cytokines were associated with decreased TREM2 signaling in late‐life major depression (LLMD).

Method

Fifty‐one cognitively‐intact subjects aged 60 years and older, completed a 3‐year longitudinal study and an optional lumbar puncture (LP). Of these individuals, 49 were included in the analysis (29 LLMD and 20 controls). Independent‐samples Mann‐Whitney‐U Tests were used to compare groups. Non‐parametric correlations were run between CSF sTREM2 and plasma IL‐1B, Il‐6, Il‐8, TNFα, and CSF C3.

Result

In LLMD, higher plasma IL‐6 (r = ‐0.45, p = 0.02) and TNFα (r = ‐0.41, p = 0.30) were both associated with lower CSF sTREM2, but not with higher CSF C3 (p = 0.19) or other pro‐inflammatory markers consistent with a reduction in TREM2 signaling. These findings were not observed for controls.

There were no group differences in Plasma IL‐1B, IL‐6, TNFα and CSF C3. Plasma IL8 was significantly higher in LLMD vs controls (p = 0.03). No correlations between plasma and CSF levels were observed for cytokines within the LLMD group.

Conclusion

Higher plasma pro‐inflammatory cytokines were associated with lower CSF sTREM2 in LLMD, consistent with a reduction in TREM2 signaling. Future studies should determine if lower CSF sTREM2 levels predict increased AD biomarkers, progressive decline and conversion to AD in LLMD.
Quadratic associations between subthreshold amyloid‐beta retention and cortical volume modulated by APOE genotype in cognitively normal older adults
Authors: Kang Dong Woo , Lim Hyun Kook , Lee Chang Uk
Published: June 2023

Background

A growing body of evidence suggests a deteriorating effect of subthreshold amyloid‐beta (Aβ) accumulation before the onset of clinical symptoms of Alzheimer’s disease (AD). Despite the association between the Aβ‐dependent pathway and the APOE ε4 allele, the modulating impact of this allele on the associations between subthreshold Aβ retention, cortical atrophy, and neuropsychological performance is unclear. This study aimed to explore the differential effect of the APOE ε4 allele on the association between subthreshold Aβ retention, cortical volume, and cognitive performance in cognitively healthy older adults (CN).

Method

A total of 112 CN with subthreshold Aβ retention, consisting of 80 APOE ε4 non‐carrier and 32 APOE ε4 carrier, were included in the study. Participants underwent structural magnetic resonance imaging, [18F] flutemetamol (FMM) PET‐CT, and neuropsychological battery. Potential interactions between APOE status and Aβ accumulation were assessed with F‐tests implemented on both linear and quadratic interaction terms, adjusting for age, sex, and education years.

Result

We found a significant interaction between APOE ε4 allele, subthreshold Aβ deposits, cognitive function for cortical volume of predefined brain regions vulnerable to early Aβ retention. In CN with APOE ε4 carrier, regional Aβ retention in frontal, parietal, temporal lobe, and posterior cingulate cortex/precuneus showed a U‐shaped relationship with cortical volumes of superior parietal, fusiform gyrus, and amygdala. Furthermore, cortical volumes of superior, inferior temporal lobe, and parahippocampal gyrus in APOE ε4 carrier displayed a U‐shaped relationship with attention and executive function scores.

Conclusion

This study is the first attempt to thoroughly examine the mechanism at play in the earliest phase of Alzheimer’s disease, focusing on the influence of the APOE ε4 allele on the association between subthreshold Aβ retention and cortical volume during the preclinical phase.
Impact of APOE ε4 allele on associations between sub‐threshold, positive Amyloid‐β retention, brain function, and cognitive performances in cognitively normal older adults
Authors: Kang Dong Woo , Lim Hyun Kook , Lee Chang Uk
Published: June 2023

Background

A growing body of evidence suggests a deteriorating effect of sub‐threshold amyloid‐beta (Aβ) accumulation on cognition before the onset of clinical symptoms of Alzheimer’s disease. Despite the association between the Aβ‐dependent pathway and the APOE ε4 allele, the impact of this allele on the progression from the sub‐threshold Aβ deposits to cognitive function impairment is unclear. Furthermore, the comparative analysis of positive Aβ accumulation in the preclinical phase is lacking. This study aimed to explore the differential effect of the APOE ε4 allele on the association between Aβ retention, brain function, and cognitive performance in cognitively healthy older adults, depending on the Aβ burden status.

Method

One hundred and eighty‐two older adults with normal cognition who underwent resting‐state functional magnetic resonance imaging were enrolled. They were dichotomized using [18F]‐labeled flutemetamol positron emission tomography into subjects with sub‐threshold (cognitively normal [CN] sub‐Aβ, n = 110; [APOE ε4 carrier, n = 30; non‐carrier, n = 80] and positive Aβ deposits [CN Aβ+ group, n = 72; APOE ε4 carrier, n = 34; non‐carrier, n = 38]).

Result

We found (i) distinct effects of the APOE ε4 allele and relationships with cognitive function in the preclinical phase; (ii) differences in local functional connectivity (FC) of the brain regions in networks vulnerable to Alzheimer’s disease according to the APOE ε4 allele, which was associated with higher executive and memory function; (iii) a differential association between regional Aβ retention and local FC according to the APOE ε4 allele; and (iv) a significant interaction between APOE ε4 allele and local FC for the remote inter‐network FC between the default‐mode and central‐executive network in the CN sub‐Aβ group, contributing a compensatory role for cognitive performance. Finally, these results were modulated according to Aβ positivity.

Conclusion

This study is the first attempt to thoroughly examine the mechanism at play in the earliest phase of Alzheimer’s disease, focusing on the influence of the APOE ε4 allele from the sub‐threshold to positive Aβ retention during the preclinical phase.
Effect of APOE e4 allele on age‐related brain FDG‐PET uptake in older individuals at risk of dementia
Authors: Khalifa Khadija Nasralla
Published: June 2023

Background

In Alzheimer’s Disease (AD) patients, accumulating evidence suggests that the APOE‐e4 allele drives amyloid and tau pathology and decreases brain glucose metabolism. Similarly, in older healthy subjects, APOE‐e4 has been linked to brain hypometabolism. However, there are scarce clinical studies concerning the effect of APOE e4 and the age‐related cerebral glucose metabolism patterns of older individuals at‐risk for dementia.

Objective

This exploratory analysis aims to study the impact of carriage of the APOE‐e4 allele on age‐related brain glucose metabolism patterns of older individuals at‐risk for dementia.

Method

54 community‐dwelling older adults aged 60‐80 years with increased risk for AD due to cardiometabolic disorders (CMD, n = 32) or mild cognitive impairment (MCI, n = 22) who participated in a clinical trial. APOE genotyping was performed to identify carriers of the APOE‐e4 allele. 18F‐Fluoro‐2‐deoxy‐D‐glucose‐positron emission tomography/computed tomography (18F‐FDG PET/CT) was conducted and mean 18F‐FDG uptakes in brain regions of interest (ROI) from the atlas of anatomical labeling were obtained.

Group differences by diagnosis (CMD,MCI) and APOE‐e4 status were examined using independent samples T‐tests. Linear regression models were conducted to evaluate the effect of age over mean 18F‐FDG uptake in each ROI. Age*APOE‐e4 interactions were examined, and the models were adjusted for diagnosis subgroup and gender effects. Adjusted models were corrected for multiple testing using the False Discovery Ratio (FDR).

Result

Mean 18F‐FDG uptake at each ROI was comparable between diagnosis and APOE‐e4 allele status groups. After correcting adjusted models for multiple testing, significant Age*APOE‐e4 interactions were found at the right inferior occipital gyrus (β ‐0.13, 95% CI ‐0.25 – 0.02, p = 0.035, FDR = 0.039), right paracentral lobule (β ‐0.14, 95% CI ‐0.25 – ‐0.03, p = 0.016, FDR = 0.024), and left superior parietal gyrus (β ‐0.11, 95% CI ‐0.20 – ‐0.02, p = 0.014, FDR = 0.021).

Conclusion

In older individuals at risk of dementia, carriage of the APOE‐e4 allele was associated with an increased age‐related reduction in mean 18F‐FDG uptake in the right inferior occipital gyrus, right paracentral lobule, and left superior parietal gyrus. Knowledge of age‐ and APOE‐e4 allele‐related cerebral metabolic changes is critical to correctly interpreting brain 18F‐FDG PET/CT findings.
Phonemic Fluency in pathologically confirmed Alzheimer’s disease (AD) versus AD with Lewy Bodies
Authors: Johnson Jordan , Fernandez Kayri K , Barker Megan S , Hernandez Michelle , Soto Elizabeth , Gu Yian , Stern Yaakov , Cosentino Stephanie
Published: June 2023

Background

Although Alzheimer’s Disease (AD) and Lewy Body Disease (LBD) have distinct underlying pathologies, the clinical differentiation of these disorders remains challenging, particularly AD versus mixed AD/LBD. Previous studies have shown that patients with mixed AD/DLB can have lower total output phonemic fluency than patients with AD. Examining the qualitative features of fluency performance may offer an even more sensitive approach to detecting group differences. One potentially useful measure is the ability to sustain generation of words over time; that is, whether a participant continues producing words across the full 60 seconds, or whether their responses “drop off”. A “drop off” in verbal generation on fluency tasks has previously been reported in Mild Cognitive Impairment due to AD. We assessed whether this qualitative phonemic fluency score would differ between autopsy confirmed AD versus mixed AD/DLB or DLB.

Method

Participants with postmortem pathological diagnoses of AD (n = 15) and DLB (mixed or pure DLB; n = 8) were included in the present study. Participants completed phonemic fluency task at their baseline visit as part of a neuropsychological battery of tests. Participants were asked to generate as many words as possible that start with a given letter in one minute across three trials (i.e., C, F, L). The drop off in phonemic fluency over time was calculated by dividing the number of words produced in the second half of the test (i.e. second 30‐second interval) by the total number of words generated across 60 seconds. Group differences were analyzed using a one‐way analysis of variance (ANOVA).

Result

Whereas total CFL score did not differ in this sample (p = .21), patients with DLB produced a significantly higher proportion of words in the second half of the CFL test (M = 0.40; SD = 0.14), compared to patients with pure AD (M = 0.27, SD = 0.10), p = 0.016.

Conclusion

Novel scoring of the CFL test may help to differentiate cases with pure AD and cases with DLB pathology. In the current study, pure AD patients had more difficulty in sustaining word generation over 60 seconds. Future research should continue to look at different ways to score and analyze neuropsychological assessments to improve early differential diagnosis.
The Covid‐19 pandemic, depression, and cognitive decline: Insights from the Srinivaspura Aging, Neuro Senescence, and COGnition (SANSCOG) study
Authors: Stezin Albert , Sundarakumar Jonas S. , Lingegodwa Abhishek Mensegere , Ravindranath Vijayalakshmi
Published: June 2023

Background

The COVID‐19 pandemic and the policies to contain it had a widespread impact on the life and livelihood of participants enrolled in the Srinivaspura Aging, Neuro Senescence, and COGnition (SANSCOG) study. We evaluated the prevalence of depression associated with the pandemic and its impact on cognition in our cohort.

Method

We used the geriatric depression scale (GDS) to objectively assess the depression scores of 400 participants before the first wave (March 2020; W1) and after the second (March 2021; W2) wave of the pandemic. We also assessed the cognitive profile of participants at these two timepoints using tests from the COGNITO battery.

Based on the GDS score, the participants were classified into three groups‐ (a) Group A: participants with depression (GDS>4) at W1 and no depression W2 assessments (b) Group B: participants without depression at W1 and with depression at W2 assessments, and (c) Group C: participants with depression at W1 and W2. In each subgroup, the neuropsychological scores were compared using the Mann‐Whitney U test.

Result

The overall prevalence of depression was 26.5%. The prevalence of depression at W1 and W2 were 12.5% and 17.7%, respectively.

The participants in group A (n = 55) had a significant increase in the reaction time between W1 and W2. In group B (n = 35), there was a significant increase in the reaction time and decrease in auditory attention, dual attention, Immediate and delayed recall scores of logical memory test, category fluency, letter fluency, and copying score in stick‐figure design test. In group C (n = 16), there was a significant increase in the reaction time and a decrease in auditory attention.

Conclusion

There was a 5.2% increase in the prevalence of depression between W1 and W2 in our cohort. The cognitive decline was more evident in participants who developed depression during the intercurrent interval between the W1 and W2.
Baseline data from the Australian PITCH study: Characteristics of home care workers providing dementia care
Authors: Goh Anita M Y , Dang Christa , Savvas Steven , Doyle Colleen , Batchelor Frances , Tan Esther , Oglivy Veronica , Duckworth Tanya , Wise Erica , Low Lee‐Fay , Dow Briony
Published: June 2023

Background

People living with dementia increasingly prefer to live in their own home as their care needs progress. Home care workers (HCWs) are essential for supporting independent living, and need training and support on how to deliver evidence‐based and best‐practice dementia care. The home care workforce is diverse, and in Australia, the number of workers who identify as culturally and linguistically diverse (CALD) in 2020 represented 21% of the total direct‐care workforce.

The Promoting Independence Through quality Care at Home (PITCH) project aims to improve outcomes for people living with dementia and their paid and family carers by co‐designing and testing an evidence‐based specialist training program for dementia care. A pragmatic stepped‐wedge cluster RCT is being conducted to evaluate the program. To date, 227 HCWs from seven home care providers across Australia have completed baseline measures.

Method

HCWs completed the Strain in Dementia Care Scale (SDCS), Sense of Competence In Dementia Care – Staff (SCIDS), Dementia Attitudes Scale (DAS) and Dementia Knowledge Assessment Scale (DKAS). Associations between these measures was assessed using Pearson correlations. HCWs were grouped into CALD/non‐CALD groups based on self‐reported cultural background. ANOVAs examined group differences by CALD status.

Result

For the whole sample, SCIDS was correlated with DAS (r = 0.599, p<0.005) and DKAS (r = 0.257, p<0.005). DAS and DKAS were moderately correlated (r = 0.334, p<0.005). Nearly 30% of HCWs in our sample identified as CALD. The CALD group showed lower DAS, DKAS and SCIDS compared to the non‐CALD group (p’s<0.001). No differences were observed on SDCS (p = 0.58).

Conclusion

HCWs who were more knowledgeable about dementia had more positive attitudes toward dementia and a higher sense of competence in dementia care. HCWs who did not identify as CALD showed greater dementia knowledge, more positive dementia attitudes, and higher sense of competence in dementia care. Findings suggest that better dementia literacy supports more positive attitudes to dementia and sense of competence, and highlights that more targeted and specialized support may be beneficial for staff from CALD backgrounds (who comprise a high proportion of the Australian aged care workforce). Findings have implications for clinicians, researchers, policy‐makers, educators, and providers of dementia services.
Kernel flow and the eye‐ brain connectome: Study design and objectives
Authors: DeBuc Delia Cabrera , Ramos Alberto R , Galor Anat , Mendoza‐Santiesteban Carlos , Sapahia Rishav , Hasalami Ardita , Fernandez Javier De Jesus , Habash Ranya
Published: June 2023

Background

More evidence suggests how the eye health may be crucial in older adults at risk of developing cognitive impairment (CI) and Alzheimer’s disease (AD). Ocular conditions and AD share several common factors, including older age behavioral and cardiometabolic disease. Poor vision can lead to reduced activation of central sensory pathways, which is associated with higher cognitive load and brain structure damage. We showed that CI is not limited to the brain but also affects the retina. However, despite recent advances in neuroimaging biomarkers (e.g., PET diagnostics), there remains a need for more readily available and affordable diagnostic testing for AD risk. While blood flow within the optic nerve head can be quantified using advanced optical imaging technologies, it is essential to measure what is going on in the brain at the same time.

Method

We propose a cross‐sectional and longitudinal, observational study evaluating structural and functional biomarkers of the retina and brain associated with AD disease risk and/or progression. The study objective is to collect structural and functional data of the retina and brain to facilitate the discovery of reliable and sensitive multimodal biomarkers of AD disease risk and/or progression. We will examine participants (N = 200) aged 55‐80; 50 cognitively healthy (CH), 50 with preclinical AD, 50 with mild CI (MCI), and 50 with mild AD. Assessments will include neuropsychological testing, medical/functional assessment, retinal imaging, brain activity, electroretinography, pupillometry, and contrast sensitivity. We will use a wearable, whole‐head coverage time‐domain functional near‐infrared spectroscopy system (Kernel Inc) to measure local changes in blood oxygenation and electroencephalography.

Result

The eye‐brain connectome is integral in understanding pathology in neurodegenerative diseases. We aim to use the eye‐brain data to develop screening and monitoring tools to identify and track AD risk and severity.

Conclusion

This study will overcome limitations for performing functional brain imaging due to the lack of portability and user‐friendliness of neuroimaging devices. Our eye‐brain multimodal biomarker study could also facilitate a novel application for diagnostic assessment and therapeutic intervention to target neuroanatomical sites compromised early in AD, leading to a more robust technique to identify high‐risk individuals before cognitive decline with sufficient sensitivity and specificity.
A comparative study of cardiovascular risk factors and its impact on cognitive function in rural and urban Indian cohorts
Authors: Jain Shubham , Lingegodwa Abhishek Mensegere , Stezin Albert , Ravindranath Vijayalakshmi
Published: June 2023

Background

The Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) risk score is used to assess the future risk of developing dementia based on cardiovascular risk factors. In this study, we compared the cognitive functions of participants with higher and lower risk of dementia assessed using CAIDE score, in the rural and urban Indian populations. Data was obtained from participants enrolled in the TATA Longitudinal Study of Aging (TLSA) and Srinivaspura Aging, Neuro Senescence, and COGnition (SANSCOG) study, which are two large, harmonized studies from urban and rural India, respectively.

Methods

The clinical and blood biochemistry data from rural (n = 2005) and urban (n = 291) participants were used to estimate the CAIDE score and classify participants as high risk (score ≥ 9) and low risk of dementia (score < 9). The neuropsychological evaluation was performed using COGNITO battery, a computerized neuropsychometric platform that tests five cognitive domains. The cognitive scores of the high‐risk and the low‐risk groups were compared.

Results

The rural cohort, compared to the urban cohort, had a lower proportion of people with formal education ≥10 years (17.0% vs. 99.3%), age above 54 years (63.5% vs. 90.8%), systolic BP > 140 mm Hg (10.1% vs. 33.7%) and BMI >30 kg/m2 (6.6% vs. 20.9%). The proportion of people with higher total cholesterol, gender distribution, and physical activity was comparable in both cohorts.

On risk stratification, the high‐risk category comprised 26.34% of the rural and 9.46% of the urban cohort. The participants belonging to the high‐risk category from the rural cohort performed poorly in all cognitive domains, compared to the low‐risk category. In the urban cohort, there was no significant difference between both groups.

Conclusion

The rural population had a higher proportion of people at high risk of dementia in the future, despite the younger age and lower proportion of participants with higher systolic BP and BMI. It seems that the lack of formal education may be primarily responsible for higher CAIDE scores in the rural population. Their baseline neuropsychological profile probably forecasts the possibility of cognitive dysfunction in the future. Interventions may help modify the cardiovascular risk factors and decrease the future burden of dementia.
Subjective and objective cognitive impairment in patients with obstructive sleep apnea
Authors: Rattanabannakit Chatchawan , Tungwacharapong Pecharut , Kuendee Sorawich , Pimolsri Chawanont , Senanarong Vorapun , Chotinaiwattarakul Wattanachai
Published: June 2023

Background

Obstructive sleep apnea (OSA) is associated with cognitive impairment (CI). We aimed to study subjective cognitive complaint (SCC) and objective cognitive scores, and its relation to polysomnography (PSG) parameters, in patients suspected of OSA.

Method

Patients suspected of OSA who were scheduled for PSG were recruited. Cognition was assessed by the Montreal Cognitive Assessment (MoCA) and the Color Trails Test (CTT). The Memory index score (MIS) was also calculated from the MoCA. The presence of SCC was assessed by asking patients directly and using the Cognitive Change Index rated by self (CCI‐S) or informants (CCI‐I). Patients with severe dementia were excluded.

Result

Among 258 patients with an age of 61.46±7.05 years, 51.2% are female. The mean MoCA was 23.89±3.89. Based on PSG, patients were classified as having no OSA to mild OSA (20.1%), moderate (28.3%), and severe OSA (51.6%). Based on cognitive tests, patients with moderate to severe OSA had a higher proportion of objective cognitive impairment (64.1%) but less SCC (38.3%) than patients with no OSA or mild OSA. CCI‐S and CCI‐I scores were significantly correlated with each other (r = 0.238, p = 0.019) but not with MoCA score nor CTT‐time. Objective cognitive tests scores were associated with the number of comorbidities and several PSG parameters, i.e., total sleep time, sleep onset latency, wake after sleep onset, sleep stages, mean O2 saturation, and time spent of SaO2 under 90% (all p<0.05). Meanwhile, subjective cognitive scores were not associated with any PSG parameters. However, the self‐report (CCI‐S) was significantly correlated with the Thai‐Geriatric Depression Scale and the Epworth Sleepiness Scale (r = 0.388 and 0.262, respectively, p <0.001). Thirty patients with severe OSA and CI were followed‐up after CPAP treatment for the mean of 12.2 months and showed a significant improvement on MoCA and MIS scores, but not the CTT and CCI scores.

Conclusion

Most patients with OSA had objective cognitive impairment, but SCC was found less in a more severe stage of OSA. Several PSG parameters were associated with cognitive scores but not subjective cognitive scores. Patients with severe OSA could have a cognitive benefit after CPAP treatment.
Hydroxy‐docosahexaenoic acid (DHA‐H) and its immediate metabolite Heneicosapentaenoic acid (HPA) exert neuroprotection and prevent amyloidogenic APP processing
Authors: Cabot Joan , Parets Sebastià , Miralles Marc , Fernández‐García Paula , Lladó Victoria , Busquets Xavier , Escriba Pablo V. , Torres Manuel
Published: June 2023

Background

DHA‐H (Hydroxy‐docosahexaenoic acid) is a molecule in development for Alzheimer’s disease (AD) treatment based on the concept of membrane lipid therapy (melitherapy). Once entered the cell, DHA‐H is metabolized via α‐oxidation to the fatty acid HPA (Heneicosapentaenoic acid). DHA‐H has been shown to reduce the amyloidogenic processing of Amyloid Precursor Protein (APP), as well as having a neuroprotective effect in cellular models. Although the mechanism of action of DHA‐H is not yet fully understood, results obtained in excitotoxicity models and lipid profile analysis suggest that HPA could be a DHA‐H effector.

Methods

: APP processing was assessed in cell cultures of HEK293 and N2a neuroblastoma cell lines and analyzed by western blot. Neuroprotective effect of DHA‐H and HPA was tested in neuron cells differentiated from SH‐SY5Y neuroblastoma cells that were stimulated with NMDA (N‐Methyl‐D‐Aspartate)/Ca to induce excitotoxicity. Lipid samples for lipid profile analysis were obtained from the same cultured cells by addition of chloroform/methanol. Fatty acids were transformed into methyl esters and analyzed by GC‐FID (Gas Chromatography‐Flame ionization detector).

Results

: DHA‐H administration decreases the levels of derivatives from the APP amyloidogenic processing. DHA‐H and HPA showed a neuroprotective effect in a neuronal model of NMDA‐induced excitotoxicity. DHA‐H administration does not significantly alter the main fatty acids but clearly increases HPA levels in the cells.

Conclusion

All these results together demonstrate that DHA‐H exerts neuroprotection and prevents amyloidogenic processing possibly through its metabolic intermediate HPA. Therefore, HPA appears as a new promising molecule for Alzheimer’s therapy.
Predicting cortical thickness with [18F]flortaucipir PET: A longitudinal MRI study
Authors: Visser Denise , Ossenkoppele Rik , Bosch Iris W.M. , Brouwer Iman , Tuncel Hayel , Coomans Emma M. , Rikken Roos M. , Mastenbroek Sophie E , Verfaillie Sander C.J. , Golla Sandeep S.V. , Barkhof Frederik , van der Flier Wiesje M. , van Berckel Bart N.M.
Published: June 2023

Background

The association between tau pathology and neurodegeneration (atrophy) in Alzheimer’s disease (AD) is not fully understood. This study aimed to investigate whether tau pathology is associated with concurrent and longitudinal cortical thickness in individuals along the AD continuum.

Method

We included 92 amyloid‐positive cognitively impaired individuals (age 65±7, 48% female, MMSE 23±4) with AD dementia (n = 73) or mild cognitive impairment due to AD (MCI, n = 19) and 61 cognitively normal individuals (CN; age 66±8, 48% female, MMSE 29±1) with subjective cognitive decline (SCD, n = 55, 19 amyloid‐positive) or healthy controls (HC, n = 6, amyloid‐status unknown). All participants underwent dynamic [18F]flortaucipir PET and structural 3T‐MRI at baseline. A subset underwent two‐year follow‐up structural 3T‐MRI (CN: n = 35, time‐interval 24±8 months; AD: n = 26; time‐interval 28±4 months). Parametric [18F]flortaucipir binding potential (BPND) images were generated using receptor parametric mapping (cerebellar gray matter reference region) to quantify tau pathology. Cortical thickness (over time) was measured using Freesurfer (version 6.0.1). Regional associations between [18F]flortaucipir BPND and cortical thickness were assessed using linear mixed models in three commonly used a priori defined regions‐of‐interest, including entorhinal, middle‐and inferior temporal, and neocortical areas. Models were adjusted for age, sex and amyloid status (in case of CN individuals).

Result

For cognitively impaired individuals, higher [18F]flortaucipir BPND (in all three regions) was associated with lower concurrent cortical thickness in the entorhinal cortex [Table‐1&Fig‐1]. Higher middle‐ and inferior temporal and neocortical BPND was associated with cortical thinning over time within the same region (intra‐regionally). Higher middle‐ and inferior temporal BPND additionally showed associations with cortical thinning over time in the neocortex (inter‐regionally). For cognitively normal individuals, we found no associations between [18F]flortaucipir BPND and cortical thickness (over time) [Table‐1&Figure‐1].

Conclusion

Tau pathology is associated with both concurrent and longitudinal atrophy in a region‐specific manner in cognitively impaired individuals (MCI/AD), but not in cognitively normal individuals (HC/SCD). The regional‐specificity of these associations might suggest that there are similarities between tau‐related progression patterns and patterns of neurodegeneration. Taking into account a temporal delay between the development of region‐specific tau pathology and neurodegeneration, this potentially suggests that tau pathology is a (partial) driver of neurodegeneration in AD.
The effect of virtual reality on executive function in older adults with mild cognitive impairment: A systematic review and meta‐analysis
Authors: Lai Frank Ho‐yin , Yu Hailey Dan , LI Xun
Published: June 2023

Background

Virtual reality (VR) ‐ a computer simulation of a real or imagined three‐dimensional (3‐D) environment, which allows users to have the same experiences they would get in a similar real situation, has stimulated the interest of researchers and clinicians since its first use in 1994. Compared to traditional pen‐and‐paper training, it is symbolized as a systematic and controllable intervention that makes use of data visualization and provides immediate feedback based on the participants’ performance. VR is usually categorized into three types according to the form of connection with the physical world, and includes non‐immersive, semi‐immersive, and full‐immersive VR.

Method

This review aimed to summarize the currently available premium evidence to determine the effect of virtual reality (VR) on executive function (EF) in older adults with mild cognitive impairment (MCI), and to detect what level of immersive VR would be the most beneficial. Five electronic databases, namely, PubMed, Embase, PsycINFO, CINAHL and Cochrane Library were searched. Our research team screened the studies and extracted data according to our inclusion criteria. The methodological quality of each study was rated using the PEDro scale. When three or more studies reported the same outcome, a meta‐analysis was conducted using Review manager 5.4.1

Result

Finally, 14 randomized controlled trials with a total of 518 participants were included. VR training had an overall positive effect on cognitive flexibility, global cognitive function, attention, and short‐term memory compared to the control groups. Additionally, semi‐immersive VR was more effective in improving cognitive flexibility compared to the other two types of VR. The application of non‐immersive level of VR had a significant effect on global cognitive function, attention, short‐term memory, and cognitive flexibility.

Conclusion

VR may be effective in improving EF in older adults with MCI. However, the level of immersive VR that would be the most beneficial on EF still needs to be investigated with a greater number of well‐designed studies.
Changes in serum urate and body weight interact to affect cognitive decline rates of community‐dwelling older adults
Authors: Nelson Kendra L , Cheatham Carol L , Voruganti Saroja
Published: June 2023

Background

Several innate and environmental factors affect the rate and degree of cognitive decline with each factor representing a potentially valuable intervention point to slow progression of this decline. Serum urate, a product of purine metabolism and potent antioxidant, and weight loss have been associated with cognitive decline. The aim of this study was to determine the relation among urate, body weight, and their interaction with cognitive function.

Methods

In the context of a larger study, 133 adults aged 65‐80 at baseline (mean baseline age 72.7 years, 56.5% male) were recruited to participate in a double‐blind, randomized controlled trial. The Montreal Cognitive Assessment (MoCA) was administered to assess cognitive function. Those with MoCA scores >25 were considered cognitively typical, whereas those with MoCA scores below this threshold were deemed to be experiencing mild cognitive decline (MCD). The cognitively typical group was instructed to maintain their regular diet and served as a reference, whereas MCD groups were randomized to receive either 35mg lyophilized wild blueberries or dextrose (serving as control) daily in addition to their regular diet. MoCA, anthropometric measures, and serum were collected at baseline and repeated at 3 and 6 months. The statistical analysis was performed using MiniTab v.19.

Results

A regression‐based analysis showed that changes in serum urate were positively associated with changes in MoCA scores (ß = 0.94, SE = 0.47, p < 0.05) at 6 months. Groupwise analyses showed that changes in MoCA scores were not correlated with changes in urate or body weight in individuals with typical cognition or those in the blueberry group. However, in the control group, changes in serum urate (ß = 1.96, SE = 0.92, p<0.05), changes in body weight (ß = ‐0.31, SE = 0.13, p<0.05), and interaction between urate and body weight significantly impacted the change in MoCA scores. (ß = 0.663, SE = 0.20, p<0.05). Individuals with increased urate and decreased body weight showed less cognitive decline as compared to those who had weight gain and decreased urate.

Conclusion

Our findings show that changes in urate and body weight interact with each other to significantly impact changes in cognitive function.