bluuebunny/crossref_metadata_2025 huggingface dataset:
APOE ε4 and cognitive networks: Centrality of episodic memory nodes in patients with mild cognitive impairment
Authors: De Marco Matteo , Wright Laura M , Valera‐Bermejo Jose Manuel , Ferguson Cameron E
Published: December 2023

Background

The literature based on univariate models does not lead to unequivocal conclusions on the effects of APOE variability on cognition. We thus hypothesised that the impact of APOE‐ε4 on cognitive functioning can be reliably captured by graph‐theory.

Method

Cognitive datasets were extracted from the National Alzheimer’s Coordinating Center’s database. After the application of stringent exclusion criteria, 16,173 participants with a known APOE ε3ε3/ε4ε3/ε4ε4 genotype were retained: 8,118 controls, 3,482 MCI patients and 4,573 AD‐dementia patients. ε3ε3 individuals were classified as “non‐carriers”, while ε4ε3/ε4ε4 individuals were tagged as “carriers”. Two independent sub‐cohorts were defined based on the version of the battery used to characterise cognitive profiles. Pairwise Markov random‐field models of cognitive functioning were constructed in “R” using the “qgraph” package, following published methodological guidelines. Nine cognitive nodes were established, and partial correlations were run to calculate the statistical strength of all node‐to‐node edges. This was regularised via the LASSO penalty‐imposing method, to control graph sparsity. Differences in global and nodal metrics between ε4 carriers and non‐carriers were tested via permutation‐based Network Invariance Tests. These analyses were run separately in each sub‐cohort and within each diagnostic status. “Expected Influence” was analysed as the centrality metric of interest, to assess how influential each node is within its network.

Result

A significant APOE‐dependant effect emerged from the analysis of the Logical‐Memory nodes in MCI patients in both sub‐cohorts. While non‐carriers showed equal centrality in immediate and delayed recall, the latter was significantly less central among carriers. These findings were replicated in the sub‐groups of sole amnestic‐MCI patients (n = 2,971), were independent of differences in network communities, clinical severity or other demographic factors. No effects were found in the other diagnostic groups or in global network metrics.

Conclusion

APOE‐ε4 influences nodal properties of cognitive networks when patients are clinically classified as MCI. Our findings expand this area of knowledge by characterising the statistical effect of the ε4 allele in terms of its differential impact on immediate and delayed recall, and how this results in specific network effects. The study of the wider cognitive network can complement univariate approaches in characterising the effects of risk factors.
Tau conformational changes in aging‐related tau astrogliopathy.
Authors: Rodriguez Roberta Diehl , Grinberg Lea T. , Suemoto Claudia Kimie , Socher Karen L R , Ferretti‐Rebustini Renata Eloah de Lucena , Leite Renata Elaine Paraizo , Jacob‐Filho Wilson , Pasquallucci Carlos Augusto , Nitrini Ricardo
Published: December 2023

Background

The presence of aging‐related tau astrogliopathy (ARTAG) is highly frequent, but poorly characterized in aging brain and neurodegeneration. Over the abnormal tau accumulation processes, tau protein undergoes pathological modifications and the sequency of these pathological events can be associated with different levels of tau aggregation.

Method

To evaluate the frequency of ARTAG in a large population‐based study, we analyzed brain sections immunostained with phosphor tau (AT8) of 1151 individuals with previous neuropathological evaluation. Further, to investigate early stages of tau protein aggregation in ARTAG, we performed additional immunohistochemistry in the amygdala of 32 cases with ARTAG pathology using the following tau antibodies: AT100 and Tau‐C3.

Result

ARTAG was frequently observed in cognitively normal individuals independent of concomitant neurodegenerative disease. Higher burden of Alzheimer‐type pathology was observed in ARTAG compared to non‐ARTAG. Also, presence of more than one pathology (mixed pathology) was higher in ARTAG compared to non‐ARTAG (p<0.001). Additionally, AT100 immunoreactive ARTAG was found in overall cases, while Tau‐C3 immunoreactive ARTAG was not observed in 12 cases (36%), showing different mature stage for ARTAG compared to neurofibrillary tangles.

Conclusion

Different immunological markers can be found in ARTAG and Alzheimer’s neurofibrillary pathology in early stages of tau pathological processing, suggesting different levels of abnormal tau aggregates among cases with ARTAG pathology.
Mapping changes in synaptic vesicle protein 2A (SV2A) in neurodegenerative diseases
Authors: Bavarsad Mahsa Shanaki , Spina Salvatore , Seeley William W. , Rabinovici Gil D. , Grinberg Lea T.
Published: December 2023

Background

Synaptic loss is an early feature of neurodegenerative diseases and the best correlate of clinical decline. Synaptophysin is a pre‐synaptic protein used as a marker of synaptic integrity. Although no biomarker is available to measure synaptic integrity in the clinical setting, various potential PET‐scan tracers are under development. Tracers to detect synaptic vesicle protein 2A (SV2A), an integral glycoprotein in the membrane of synaptic vesicles, are among the most promising among those in development. However, the topographical distribution of SV2A in the human brain and the degree of regional changes in different neurodegenerative conditions are unclear, making it challenging to establish the utility of SV2A tracers in clinical practice. To close this gap, we mapped the density of SV2A in five areas vulnerable to age‐related neuropathology in postmortem brain tissue of subjects with four different types of neurodegenerative disease and healthy controls. Furthermore, we compared SV2A maps to synaptophysin maps obtained from adjacent slides.

Method

Table 1 details the subjects' features. The regions of interest include middle and inferior frontal gyri, inferior temporal gyrus, angular gyrus, and CA1 sector/entorhinal cortex. 8 µm thick FFPE adjacent slides underwent immunohistochemistry for SV2A (1:150, Atlas Antibodies, rabbit polyclonal) or synaptophysin (1:75, Atlas Antibodies, rabbit polyclonal). All slides were scanned using a calibrated Zeiss Axioscan and quantified using the Zen software. Density was measured in 40 cortical ROIs (20 white & 20 gray matter) per area/case, randomly distributed. Values were normalized for white matter intensity.

Result

SVA2 loss was present in all disease conditions. The pattern of change was region and disease‐specific (Fig 1). Interestingly, the correlation between SV2A and synaptophysin density was poor to moderate (Fig 2).

Conclusion

Reduced SV2A expression/level in all diseases indicates that SV2A is a potential marker to detect neurodegeneration. However, the lack of correlation between synaptophysin and SV2A level changes suggests that these markers signal different pathways. Additional research is needed to investigate the relationship between regional loss of SV2A and its potential significance as a marker for neurodegenerative disorders. We are performing Western blotting and autoradiography in the same samples to confirm the immunohistochemistry findings.
White matter hyperintensity burden does not differentiate SuperAgers from average cognitive agers
Authors: Martersteck Adam , Gutstein Daniel , Sridhar Jaiashre , Zemlock Deborah , Mesulam Marsel , Rogalski Emily J
Published: December 2023

Background

The amount of white matter hyperintensity (WMH) found on T2‐weighted imaging has shown a strong relationship with age and is thought to be a marker of ischemia‐associated demyelination or secondary axonal degeneration associated with neurodegenerative disease. Previous healthy older aging studies have shown increased WMH are associated with poorer episodic memory performance and decreased volume of medial temporal lobe regions. Here, we examine if lower WMH are associated with a phenotype of successful cognitive aging, SuperAging. SuperAgers are participants over the age 80 with episodic memory at least as good as that of average middle‐aged adults.

Method

We quantified the WMH volume from T2‐FLAIR imaging with a pre‐trained Bayesian 3D U‐Net convolutional neural network in SuperAgers and cognitively healthy elderly controls (EC) of a similar age and education. All participants underwent the ADNI‐3 FLAIR on the same 3T Prisma MRI. WMH volume was square root transformed to account for the skewed distribution. A 2‐tail independent samples t‐test evaluated the difference in WMH volume between SuperAgers and EC. Additionally, we examined if there were differences within SA and EC groups by sex.

Result

46 SuperAgers (average age 86.3 ± 1.86; average years of education 16.9 ± 1.9) and 25 EC (average age 87.1 ± 5.17; average years of education 17.1 ± 3.1) met criteria and were included in the study. There was no significant difference in the volume of WMH between SuperAgers and ECs (t = 1.01, p = 0.32). Further, there was no significant difference in WMH by sex within the SuperAging group (t = 0.10, p = 0.92) or EC group (t = 0.82, p = 0.42).

Conclusion

Resistance to the development of WMH, a cross‐sectional marker of cerebrovascular disease and demyelination, does not appear to be a strong discriminating factor in 80+ year‐olds with superior memory function compared to cognitively average agers. Future analyses will include longitudinal changes in WMH and examining regional WMH. Cognitive aging is associated with several underlying brain‐based etiologies, and SuperAging may be better explained by a more sophisticated multi‐modal approach.
Dysphagia Outcomes from a Multidisciplinary Clinic for Persons with Dementia
Authors: Yee Joanne P. , Brates Danielle , Barczi Amelia , Mackowicz‐Torres Meredith , Clark Lindsay R. , Wanninger Ellen , Lewis Brian Lee Young , Kuntz Aaron , Robison Raele Donetha , Gustafson Sara , Kind Amy J. , Rogus‐Pulia Nicole M.
Published: December 2023

The Cognitive Care Clinic (CCC) provides multidisciplinary evaluation for Veterans with dementia and their care partners. Swallowing dysfunction (dysphagia) is estimated to be highly prevalent in this population. However, dysphagia is often considered an end‐stage sequelae of disease progression. Speech‐language pathology (SLP) has been incorporated into the CCC team to facilitate pro‐active dysphagia diagnosis and management. The purpose of this study was to describe the frequency of dysphagia in persons with dementia (PWD) seen in CCC and to determine relationships among patient report of dysphagia and clinical screening results.

Multidisciplinary assessments led to consensus diagnosis of dementia subtype. Validated dysphagia screening tools included the Eating Assessment Tool‐10 (EAT‐10), water swallow test (WST), and Test of Masticating and Swallowing Solids (TOMASS). Descriptive statistics were calculated for dementia subtype, stage, and dysphagia measures. Independent samples t‐tests were used to compare the relationship between patient‐reported dysphagia symptoms (mean EAT‐10 scores) with risk for aspiration (WST results).

71 Veterans with dementia were evaluated between 2017 and 2022 (mean age = 77, 4% female). The majority had Alzheimer’s disease or mixed etiology (68%) and were in the mild disease stage (52%) using the Functional Assessment Staging Tool. 16 of 58 patients (28%) who completed the EAT‐10 scored 3 or higher indicating risk for dysphagia. 23 of 68 patients (34%) failed the WST. There were no significant differences in EAT‐10 scores between those who passed and failed the WST (mean = 1.4; SD = 3.4 versus mean = 2.8; SD = 2.7). 31 of 63 patients (49%) demonstrated inefficient mastication based on length of total masticatory time on the TOMASS.

We found that over half of this predominantly mild‐stage cohort demonstrated clinical signs or reported symptoms of swallowing impairment. This suggests that dysphagia occurs at earlier stages, which is in contrast to typical beliefs about when changes to swallow function present in PWD. Additionally, there were no differences in EAT‐10 scores based on WST outcome and average EAT‐10 scores were low overall, suggesting possible underreporting of dysphagia. Findings from this novel clinic highlight the necessity of incorporating SLPs as part of a dementia care team to provide early identification and management of dysphagia in PWD.
Interference and Facilitation Effects on Stroop‐like Tasks in Older Adults
Authors: Baldo Juliana , Hall Kathleen , Chok Jas M. , Herron Timothy J , Curran Brian , Lwi Sandy J. , Blank Michael , Williams Garrett , Geraci Kristin , Sucich Gabriel , Schendel Krista , Santavicca Isabella , Thomas Lexie , Pebler Peter , Woods David L.
Published: December 2023

Background

The effect of aging on susceptibility to interference on Stroop‐like tasks is not clearly understood. Some previous studies have suggested slowed reaction time explains age‐related diminution on Stroop performance, while more recent meta‐analyses suggest that disproportionate interference effects are seen with aging, regardless of slower reaction times. In addition, other variables such as education and IQ have been suggested to mediate Stroop‐like effects in older participants.

Method

In the current study, we assessed the relationship between age and Stroop effects in 348 participants, aged 40‐89, with a wide range of educational achievement. The Stroop tasks were administered as part of a novel computerized neuropsychological battery that utilizes advanced automatic speech recognition and transcription software, the California Cognitive Assessment Battery (CCAB). We are currently utilizing the CCAB to track changes in cognition associated with aging, including evolution of mild cognitive impairment (MCI) and dementia, in an ongoing longitudinal study.

Result

Multiple regression analysis showed that age independently predicted both Stroop interference (incongruent minus neutral response times) and facilitation effects (neutral minus congruent response times). However, other variables including gender and vocabulary also independently predicted Stroop facilitation, while gender also independently predicted Stroop interference.

Conclusion

In summary, while aging has a significant impact on interference and facilitation effects on Stroop‐like tasks, additional variables such as gender and vocabulary (a proxy for IQ) also play a role in performance on these measures of selective attention.
Plasma biomarkers across the Alzheimer’s disease continuum in the New Zealand‐Dementia Prevention Research Clinics
Authors: Cawston Erin E , Griner Leon , Wong Celestine YE , Myall Daniel , Ashton Nicholas J. , Blennow Kaj , Zetterberg Henrik , Williams Joanna M , Cutfield Nicholas J , Anderson Tim J , Dalrymple‐Alford John C , Tippett Lynette J ,   The New Zealand‐Dementia Prevention Research Clinics, New Zealand
Published: December 2023

Background

Advances in ultra‐sensitive immunoassay methods, like Single molecule array (Simoa) technology, show that Alzheimer’s disease (AD) neuropathology can be detected in blood at the earliest stages of AD. This study compared cross‐sectional biomarker profiles for participants from the New Zealand‐Dementia Prevention Research Clinics (NZ‐DPRCs) who spanned the continuum from healthy older adults to a clinical diagnosis of AD.

Method

Blood plasma samples were obtained from 253 NZ‐DPRC participants (aged 55 to 87) from their baseline assessment. Participants were classified as cognitively normal adults (CN, n = 34), subjective cognitive decline (SCD, n = 64), non‐amnestic mild cognitive impairment (single and multi‐domain, non‐aMCI, n = 23), amnestic MCI (single and multi‐domain, aMCI, n = 105), and AD (n = 27). Six plasma biomarkers were selected for quantification by the HD‐X Simoa analyser (Quanterix, Billerica, MA; University of Gothenburg, Sweden): AD biomarkers amyloid‐beta peptides (Aß1‐40; Aß1‐42) and phosphorylated tau species (p‐tau181; p‐tau231); neurofilament light (NfL), for general neuronal damage; and glial fibrillary acidic protein (GFAP), for astrocyte activation. Clinical, imaging and genetic demographic data were assessed in relation to the plasma biomarkers.

Result

Plasma biomarkers across the five groups (figure 1) were assessed by linear regression adjusted for age and sex. P‐tau181, p‐tau231, GFAP and NfL were natural log‐transformed to approximate normality and improve homogeneity of variance. Biomarkers p‐tau181, p‐tau231, GFAP, NfL, Aß1‐42/Aß1‐40 ratio and Aß1‐42, all showed group effects (P < 0.05; Aß1‐40, p<0.08). Tukey’s HSD post‐hoc test for pairwise group comparisons showed significant differences in GFAP for AD vs CN, SCD, non‐aMCI as well as SCD vs MCI (P < 0.05); p‐tau181 for AD vs CN and SCD (P < 0.05); p‐tau231 for AD vs non‐aMCI (P < 0.05); Aß1‐42 for aMCI vs CN and SCD (P < 0.05); Aß1‐42/Aß1‐40 ratio for SCD vs aMCI (P < 0.05). ROC analysis will be reported for the diagnostic accuracy of these blood analytes.

Conclusion

Simoa‐quantitated blood biomarkers in the NZ‐DPRC cohort differentiates clinical groups spanning the AD continuum cross‐sectionally.
Correlation between fMRI complexity and cognition in early‐onset Alzheimer’s disease
Authors: Jann Kay , Wang Danny J.J. , Ringman John M
Published: December 2023

Background

Resting state fMRI (rs‐fMRI) studies in Alzheimer’s disease (AD) have shown that the functional connectivity (FC) of resting brain networks is progressively diminished in subjects with mild cognitive impairment (MCI) and AD. However, FC analysis of rs‐fMRI has limited capability to characterize the dynamic fluctuations of rs‐fMRI signals that possess clinically meaningful information. Recently the use of entropy measures as indices of the complexity of rs‐fMRI time‐series that provide alternative and complementary information to current fMRI‐based approaches has been proposed. Unlike FC that relies on the parcellation of nodes or selection of seed regions for network analysis, entropy measures of rs‐fMRI can be calculated on a voxel‐wise basis across the whole brain.

Method

Here we investigated the correlation between cognitive performance and rs‐fMRI complexity in a sample of 35 participants (Table1) from the Estudio de Enfermedad de Alzheimer en Jalisciences (EEAJ) project that recruits Latino persons (age 18‐80 yrs) at‐risk for fully‐penetrant ADAD. Imaging data underwent standard preprocessing. Multi‐scale entropy was calculated using Sample Entropy at 6 temporal scales using a pattern matching threshold of m = 2 and sensitivity threshold of r = 0.5. Voxel‐wise partial Spearman‐rank correlation was used to assess the relation between cognitive scores (MoCA, Trails‐B and Reverse Digit Span) including age and gender as covariates.

Result

We found significant positive associations between fMRI complexity and all three cognitive scores across the study cohort. We did not observe any significant negative correlations. The maps for MoCA and Trails‐B show areas in the anterior cingulate cortex (ACC), bilateral dorsolateral prefrontal cortex (dlPFC) and bilateral parietal cortex. Trails‐B additionally revealed areas in the insular cortex and temporal cortex. For Reverse Digit Span the correlation was more widespread and also showed associations in motor and supplementary motor cortex beside dlPFC and parietal cortex.

Conclusion

Across three cognitive tests we observed positive correlation with fMRI complexity in areas representing brain networks involved in executive function and memory processes. Impaired cognitive function thus is represented by reduced fMRI complexity. fMRI complexity might provide a novel imaging metric that is indicative of impaired cognitive function and is complementary to existing imaging approaches.
How do people with young onset dementia use technology in the workplace?
Authors: Kokorelias Kristina Marie , Bak Katherine , Nygard Louise , Mäki‐Petäjä‐Leinonon Anna , Nedlund Ann‐Charlotte , Issakainen Mervi , Ryd Charlotta , Boger Jennifer , Astell Arlene J.
Published: December 2023

Background

People who develop young onset dementia while they are working face multiple challenges staying in employment. Technology could provide some support for example, scheduling, tracking, and completing tasks, depending on occupation and environment. This study aimed to learn from the experiences of people with young onset dementia.

Method

We interviewed 28 people with young onset dementia in three countries as part of a larger study into their experiences in the workplace, including the use of technology.

Result

The interviews revealed a number of barriers and facilitators to workplace technology relating to usability, accessibility, and cognitive demands. Technology was used for a variety for tasks and participants shared adaptations they made using everyday technologies to support them in carrying out their jobs.

Conclusion

The needs of individuals with young onset dementia for technology in the workplace has so far been under explored in terms of research. Much can be learnt from the workplace experiences of people with young onset dementia to promote development of technological supports alongside other accommodations.
Increasing the influence of the Alzheimer’s research community in shaping the public narrative around AD interventions
Authors: Hendrix Kent , Dickson Samuel P. , Knowlton Newman , Hennessey Sean , Nicodemus‐Johnson Jessie , Hendrix Suzanne B.
Published: December 2023

After decades of failure in AD drug development, recent approvals signal a shift. The information associated with a new drug approval is scientifically complex and inaccessible to the general public. Historically, clinical researchers publish in scientific journals and rely on clinicians to distribute this information to the public. But with approximately 86%1 of Americans getting news from digital sources, social media has a large influence on public opinion of scientific topics. This influence was seen during the COVID pandemic and with the aducanumab approval. Many of the loudest voices are not scientifically motivated and may have conflicts of interest. It’s important to provide scientific voices.

Method: A literature search identified concerns with dissemination of scientific information through social media. Best practices are described for educating the public on scientific topics and building public trust in science. In this context, we evaluate the current transition being experienced in the Alzheimer’s field, and lessons learned over the past several years.

Result: Critical issues are: the lack of quality control of results, the tendency to believe the loudest voices, and unreported conflicts of interest. Due to the many failures in the Alzheimer’s field, many are vocal critics all AD data and the tendency is to maintain this negative approach. Many of the social media voices in the Alzheimer’s space have not been involved in AD research and may misrepresent results.

Scientist Veerasathpurush Allareddy observed “On social media, scientists have to be clear and succinct, an incentive to eliminate jargon and streamline the message.”3

Conclusion: As a field of AD researchers, we have an imperative to help shape the discussion around treatments in Alzheimer’s disease with clear, accurate and usable information. We can also encourage people in our communities to help us spread accurate scientific information as it becomes available to our research community.

1. “More than eight‐in‐ten Americans get news from digital devices” https://www.pewresearch.org/fact‐tank/2021/01/12/more‐than‐eight‐in‐ten‐americans‐get‐news‐from‐digital‐devices/

2. Huber B, Barnidge M, Gil de Zuniga H, Liu James. “Fostering public trust in science: The role of social media. https://www.researchgate.net/publication/335652963_Fostering_public_trust_in_science_The_role_of_social_media

SCIENCE “Social media: Good or evil?” 10 Feb 2022 Vol 375, Issue 6581 pp. 608‐609 https://doi.org/10.1126/science.abo2409
Memory Screening in the Community: Increasing access to early detection, diagnosis, and care
Authors: Yang Kao Lee , Kelble Laura M. , Felten Kristen , Carlsson Cynthia M , Clark Lindsay R.
Published: December 2023

Community‐based memory screening may reduce barriers and increase access to earlier diagnosis and care of Alzheimer’s disease and related dementias (ADRDs). The Memory Screening in the Community program was developed to provide cognitive screens for community members (“customers”) through Aging & Disability Resource Centers (ADRCs) across the state of Wisconsin. We evaluated program results for screens completed between 2/2022‐12/2022.

Trained ADRC staff administered a Memory Screening survey to customers during memory screening events, walk‐ins, or scheduled appointments. The Memory Screening survey collected site information, appointment type, demographics, living arrangements, and reasons for screen. Staff administered the Mini‐cog, Animal Naming, and/or AD8 instruments. Upon screen completion, staff indicated whether they recommended customers seek follow‐up evaluation with their primary care providers (PCPs) and provided education. After 6‐9 months, staff followed up with customers who received referrals over telephone to gather post‐screening and outcomes information.

647 surveys were completed across 39 counties and 5 tribal communities in Wisconsin (Figure 1). Most (∼52%) evaluations were conducted during a memory screening event and 37.4% of screens were completed due to customer memory concerns. Most customers were White (93.7%), women (70.2%), and between 70‐79 years old (31.7%; see Table). Screen results from 214 customers suggested potential cognitive impairment and they were recommended to follow‐up with their PCPs. Most memory screens included discussions about brain health, potential causes of symptoms, dementia warning signs, and importance of early detection (Figure 2). Of customers who were referred to PCPs and agreed to follow‐up calls (n = 166), 20 have completed follow‐up calls (data collection ongoing). Of these 20, 60% (n = 12) met with their PCPs, and 42% (n = 5) received a dementia diagnosis.

The Memory Screening in the Community program is feasible and has potential to provide access for cognitive screening and dementia education, especially among rural communities. In addition, roughly 1/3 of all customers screened were referred to a provider. Preliminary follow‐up data suggests community‐screening programs could facilitate diagnostic evaluation and results will be updated with a larger follow‐up sample. Overall, this evaluation demonstrates that community memory screening programs may be an effective first‐line approach in addressing ADRD‐related concerns in the community.
Genome‐wide association study of brain MRI and other phenotypes in the Tohoku Medical Megabank Organization
Authors: Taira Makiko , Saykin Andrew J. , Fuse Nobuo
Published: December 2023

Background

The Tohoku Medical Megabank Organization (ToMMo) is a large cohort study and biobank established in 2013 in the Miyagi Prefecture of Northern Japan following the Great East Japan Earthquake and Tsunami. ToMMo enrolled 150K individuals in a planned longitudinal study aiming to reveal numerous and diverse biological, psychological, and lifestyle characteristics associated with important diseases, and it collects and analyzes a rich set of biological data, including genomics, from participants to support innovative research on these diseases. Importantly, aging and Alzheimer’s disease are key areas of our research agenda, but little is known about common genetic variants that affect quantitative traits related to AD in Japanese people. MRI brain scans and cognitive screening on 12,164 cohort participants were collected at baseline (the TMM Brain‐MRI Study) since 2014 to 2019.

Method

The TMM Brain‐MRI study acquired multiple MRI sequences, including T1‐weighted imaging (T1WI). The ADNI Phantom was used, and each scan’s quality was checked. Following pre‐processing steps, Freesurfer (v7.2.0) was used with the Destrieux or Desikan‐Killiany atlas to parcellate multiple anatomical brain regions and derive cortical thickness data. We conducted a Genome‐Wide Association Study (GWAS) on all Brain‐MRI Study participants who were also genetically profiled with a Japanese‐oriented microarray (Japonica‐Array® v1, v2 and NEO) and WGS.

Result

Along with the other data types, the genotyping data for the TMM Brain‐MRI study participants represented etiological characteristics. The attached Figure shows the age distribution by decile for 7,630 male and female participants who were profiled with the Japonica‐Array® v2. The usable archived volumetric T1WI data demonstrated inverse correlations between brain volume and age, as well as very good agreement with correlations observed in previous clinical studies. We identified nominally genome‐wide significant loci (P < 5×10−8) associated with imaging phenotypes in this sample consisted of Japanese adults as the discovery stage of the study.

Conclusion

The ToMMo MRI and genetic data provide insights into the genetic architecture of the brain that are relevant to understanding brain aging and AD. Our results require some replication stages and meta‐analyses using samples of Japanese individuals in other studies.
Investigating the relationship between sleep disturbances and white matter hyperintensities in healthy older adults, MCI, and AD
Authors: Kamal Farooq , Dadar Mahsa
Published: December 2023

Background

Recent studies have shown sleep disturbances occur in people with Alzheimer’s disease (AD), with sleep being impacted before the onset of clinical symptoms. White matter hyperintensities (WMHs) are cerebrovascular disease‐related pathological changes that develop with increased age and are also associated with AD. While studies have shown that sleep disturbance can have profound negative effects on brain vasculature, its impact on WMH remains relatively unexplored. Our objective was to examine the relationship between sleep disturbances and WMHs in older adults. This study examined sleep disturbance and regional WMH differences between normal controls (NCs), people with mild cognitive impairment (MCI), and Alzheimer’s disease (AD).

Method

We included participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). History of insomnia was extracted from the ADNI database along with the Neuropsychiatric Inventory Sleep (NPI sleep) Questionnaire used to assess sleep disturbance. Participants were included if they had at least two WMH measurements and completed the NPI. A total of 1782 participants with 8771 follow‐ups met the inclusion criteria. Linear mixed‐effects models examined group differences in sleep disturbance and insomnia and the association between WMH burden and sleep in NC, MCI, and AD.

Result

People with more sleep disturbance were found to have a greater WMH burden across all regions except temporal (p < .05). People with AD and MCI had more sleep disturbance than NC across all regions (p < .0001). Additionally, people with insomnia were found to have greater WMH burden across all regions (p < .001).

Conclusion

These results suggest WMH burden and sleep disturbance increases from aging to AD. These findings indicate that people with MCI and AD with worse sleep have a higher WMH burden. In older adults, insomnia and sleep disturbances are strongly associated with increased WMH accumulation over time.
Deep Learning Derived Visceral Abdominal Fat Predicts Brain Atrophy at Midlife in 10,001 Individuals
Authors: Raji Cyrus A. , Meysami Somayeh , Hashemi Sam , Garg Saurabh , Akbari Nasrin , Gouda Ahmed , Chodakiewitz Yosef Gavriel , London Sean , Nguyen Thanh Duc , Merrill David A. , Attariwala Raj
Published: December 2023

Background

Visceral abdominal fat can predict health outcomes with increasing interest in applications on brain health.

Method

A total of 10,001 healthy participants from four sites were scanned on 1.5T MR machines with a short whole‐body MR imaging protocol. Core whole body sequences included coronal T1, STIR from vertex to feet, whole‐body axial DWI from vertex to proximal‐thighs and axial T2 TSE without fat suppression from skull base to pelvis. Brain sequences were T1 MPRAGE and 2D FLAIR. Deep learning with FastSurfer trained on 134 participants aged 27‐66 and segmented 96 brain regions. A separate deep learning model was trained to segment abdominal visceral fat from the whole‐body coronal T1. Partial correlation analysis of visceral abdominal fat volume and brain volumes were evaluated, controlling for age, sex, and total intracranial volume. Benjamini‐Hochberg False Discovery Rate of 5% controlled for multiple comparisons. Logistic regression models determined risk of brain total gray and white matter atrophy based upon the highest quartile of visceral fat and lowest quartile of these brain volumes.

Result

This cohort had an average age of 52.97 ± 13.04 years with a range of 11‐97 years with 52.8% men and 47.2% women. Mean visceral abdominal fat was 3417.81 ± 514.88 ml for overweight persons (BMI ³ 25) and 5355.24 ± 505.04 for obese persons (BMI ³ 30). Even accounting for co‐variates and multiple comparisons, deep learning segmented visceral abdominal fat predicted atrophy in multiple brain regions including: total gray matter volume (Partial R = ‐.09, p = 1.17e‐19), total white matter volume (Partial R = ‐.09, p = 2.25e‐21), hippocampus (Partial R = ‐.02, p = .005), frontal cortex (Partial R = ‐.09, p = 1.79e‐19), temporal lobes (Partial R = ‐.12, p = 2.6e‐30), parietal lobes (Partial R = ‐.04, p = .0004), occipital lobe (Partial R = ‐.03, p = .002), orbital frontal cortex (Partial R = ‐.09, p = 3.76e‐21). Visceral fat predicted increased risk for lower total gray matter (age 20‐39: OR = 5.9; age 40‐59, OR = 5.4; 60‐80, OR = 5.1) and white matter atrophy: (age 20‐39: OR = 3.78; age 40‐59, OR = 4.4; 60‐80, OR = 5.1).

Conclusion

Deep learning determined increased visceral abdominal fat volume predicts brain volume loss and may represent a novel modifiable factor in determining brain health.
Handwriting characteristics analysis for Alzheimer’s Disease and Mild Cognitive Impairments Assessment
Authors: Thebaud Thomas , Chen Casey , Moro‐Velazquez Laureano , Dehak Najim , Oh Esther S
Published: December 2023

Background

Motor changes are early signs of neurodegenerative diseases such as Alzheimer’s disease (AD), but they are often difficult to detect, especially in the early stages. In the past, the examination of handwriting has been used to investigate motoric changes in different neurodegenerative diseases. In this study, we explore a wide array of explainable characteristics of the handwriting of patients obtained with signal processing, and study their potential for assessment of Mild Cognitive Impairment (MCI) and AD.

Method

We collected the written tasks from 37 participants, 7 with AD, 17 with MCI, and 13 for the control group (CTL) on a digital tablet. We analyzed 14 different tasks, including holding the pen over a point, copying images, free writing/drawing, and memory copying. We extracted multiple movement characteristics, including the length of each stroke, the ratio of the time the pen spent on‐air vs in‐tablet and the standard deviation of the distance between consecutive points. The drawings of each subject were manually supervised, then processed to extract multiple characteristics, and compared to identify the ones providing the most significant differences between the three studied groups using Welch’s t‐test, with false discovery rate (FDR) correction.

Result

Preliminary results showed that the ratio between the time with the pen in contact with the tablet and without (on‐air vs in‐tablet) for writing tasks, significantly differentiate between AD and CTL patients (p‐value<0.01), as well as the position standard deviation when asked to maintain the pen at a fixed position (p‐value<0.05).

The comparison between MCI and CTL populations also showed that the length of the strokes for drawings and copying tasks can deliver clues to distinguish both groups (p‐value<0.05).

Conclusion

Automated analysis of a large variety of handwriting segments employing machine learning techniques can provide an assessment of patients with AD and MCI that may be useful in their early diagnosis and assessment of progression.
Workplace accommodations for individuals with dementia: experiences from three countries
Authors: Bak Katherine , Kokorelias Kristina Marie , Nygard Louise , Issakainen Mervi , Mäki‐Petäjä‐Leinonon Anna , Nedlund Ann‐Charlotte , Ryd Charlotta , Astell Arlene J.
Published: December 2023

Background

Individuals who develop Young Onset Dementia (YOD) or Mild Cognitive Impairment (MCI) when they are working, experience difficulties completing work tasks. Most legislative guidelines for workplace accommodations, are geared toward physical and mental health problems, and are not easily transferable to individuals with cognitive impairments. This study aimed to explore workplace accommodations for individuals living with YOD to maintain meaningful work.

Method

Semi‐structured interviews about their experiences at work were conducted with 28 individuals in Canada, Finland, and Sweden.

Result

Thematic analysis uncovered an overarching theme of ‘workplace context’ plus cross‐cutting themes of ‘adapted accommodations’, ‘preparing for the future’, and ‘perceptions of support’. Factors relating to job role, organization, workplace culture, and workplace relationships influenced whether support was received.

Conclusion

People who develop MCI or dementia whilst working require accommodations and support from their employers to maintain meaningful work and prepare for an uncertain future. Currently there is a lack of specific resources and policies on supporting individuals with YOD in the workplace, with individuals frequently making their own adaptations.
Experiences of Discrimination and Interest in Alzheimer’s Disease Predictive Testing in the Health and Retirement Study
Authors: Hill‐Jarrett Tanisha G , Choi Minhyuk , Buto Peter , Sims Kendra D , Miramontes Silvia , Thomas Marilyn D , Yang Yulin , Kim Min Hee , Glymour M. Maria
Published: December 2023

Background

Rapid developments in Alzheimer’s disease (AD) biomarker research suggest predictive testing may soon become a feasible option available to the public. Future reduction of racial and ethnic disparities in AD requires understanding of potential differences in drivers of interest in AD diagnostic testing. Experiences of discrimination may influence attitude toward AD testing, particularly among racially and ethnically minoritized populations. This study examines whether everyday or lifetime discrimination shapes interest in AD predictive testing.

Method

Data were collected from 1,472 participants in the 2010 and 2012 waves of the Health and Retirement Study who answered a module on interest in receiving a free test that could tell whether they would develop AD in the future, along with measures of Everyday Discrimination and Lifetime Discrimination. Logistic models were controlled for deciles of propensity scores (estimated using demographic and socioeconomic variables) and odds ratios were re‐expressed as risk differences (RD). The RD is the difference in the probability a person expressed interest in receiving a future AD predictive test based on past experiences of discrimination.

Result

The mean age of the sample was 67 (SD = 10.2), 65.9% were white, and 80% endorsed interest in AD predictive testing. Most (64.1%) participants indicated experiencing everyday discrimination in at least one domain, and 34.8% experienced major lifetime discrimination in at least one domain. Those interested in predictive testing were younger (66 vs 70 years) and more likely to be Black (20% vs 15%) or Latinx (14% vs 8%) than participants uninterested in testing. The probability of wanting an AD test was not associated with discrimination experiences for Black (RD everyday discrimination = 0.104, p = 0.285; RD lifetime discrimination = ‐0.038; p = 0.626) or Latinx (RD everyday discrimination = ‐0.003, p = 0.974; RD lifetime discrimination = ‐0.053; p = 0.692) participants.

Conclusion

Despite historical and contemporary experiences of discrimination, Black and Latinx individuals express interest in AD testing. This finding implicates structural and systemic barriers, such as systemic racism and institutional gaps in access to clinical research, as likely explanations for underrepresentation of racially and ethnically minoritized persons in research on AD testing.
Neurodegenerative biomarkers of A‐T+ compared to A+T+ and A‐T‐ older adults
Authors: Jung Joon Hyung , Yi Dahyun , Byun Min Soo , Kong Nayeong , Chang Yoon Young , Keum Musung , Jung Gijung , Ahn Hyejin , Lee Jun‐Young , Lee Yun‐Sang , Kim Yu Kyeong , Kang Kyoung Mi , Sohn Chul‐Ho , Lee Dong Young
Published: December 2023

Background

Primary age‐related tauopathy (PART) is a neuropathological entity with neurofibrillary tangles in the absence of beta‐amyloid plaques in the brain. Recent advances in neuroimaging made it possible to identify amyloid PET‐negative (A‐) tau PET‐positive (T+) condition as a possible candidate for PART in living human brains. We tried to investigate neurodegenerative biomarkers of A‐T+ older adults compared to those of A+T+ and A‐T‐ [corresponding to Alzheimer’s disease (AD) and no AD pathology, respectively] individuals.

Method

A total of 156 older participants (64 cognitively normal, 43 mild cognitive impairment (MCI), and 49 dementia), were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE). All participants underwent comprehensive clinical evaluation and multimodal brain imaging including amyloid and tau PET, and MRI. Global PiB retention measured by 11C‐PiB‐PET and tau deposition in the regions corresponding to Braak stages measured by 18F‐AV‐1451 PET were used in this study. A+ was defined as global mean Aβ deposition standardized uptake value ratio (SUVR) > 1.4 and T+ was defined as tau burden corresponding to Braak stages I/II, III/IV, or V/VI. Hippocampal volume, AD‐signature cortical thickness (AD‐CT), AD‐signature cerebral glucose metabolism (AD‐CM) and white matter hyperintensity (WMH) volume were also measured as neurodegenerative biomarkers. Multiple linear regression analysis controlling for age, gender, and APOE ε4 positivity was used to investigate the group differences of neurodegenerative biomarkers.

Result

Of the 156 participants, 31 were defined as A‐T‐, 53 as A+T‐, and 72 as A+T+. A‐T+ group had higher levels of hippocampal volume (B = 683.448, p<0.001), AD‐CT (B = 0.267, p<0.001) and AD‐CM (B = 0.174, p<0.001), but not WMH volume (B = ‐1.188, p = 0.651), compared to A+T+ group. When compared to A‐T‐ group, A‐T+ group did not show significant difference in any of the neurodegenerative biomarkers.

Conclusion

Our findings suggest that, in regard of neurodegeneration, older adults with A‐T+ condition, close to pathological PART, are less severe than those with A+T+, while they appear similar to those with A‐T‐.
MicroRNA cargo in neuron‐derived small extracellular vesicles as a novel peripheral biomarker of brain insulin resistance and related cognitive impairment in patients with type 2 diabetes
Authors: Cleary Jacob Alexander , Kumar Ashish , Su Yixin , Howard Marjorie , Hayden Kathleen M. , Ding Jingzhong , Espeland Mark A. , Deep Gagan
Published: December 2023

Background

Brain insulin resistance (bIR) is a critical risk factor for Alzheimer’s disease (AD); however, its relationship with peripheral insulin resistance remains unknown without blood‐based biomarkers to assess bIR. Here, we isolated highly pure neuron‐derived small extracellular vesicles (NDE) from plasma and characterized them with a panel of miRNAs related to bIR and cognitive impairment.

Method

Plasma samples were obtained from the Look AHEAD‐MIND study with 28 cognitively normal subjects (18 female and 10 male) and 28 subjects with probable dementia (11 female and 17 male). This study was designed to investigate the effect of sustained weight‐loss interventions on cognitive trajectories in overweight/obese type 2 diabetics (T2D). NDE were enriched from plasma sequentially using L1CAM and synaptophysin surface markers by immunoprecipitation. The expression of specific miRNAs related to bIR (miR16‐5p, miR98‐5p, miR138‐5p, miR139‐5p, miR185‐5p, and miR342‐3p) and cognitive impairment (let7a‐5p, miR9‐5p, miR15b‐5p, miR29a‐5p, miR106‐5p, miR107, miR125b‐5p, and miR210‐3p) were analyzed by RT‐qPCR and correlated with corresponding clinical measures (MMSE score, Aβ1‐40, and Aβ1‐42 expression).

Result

The expression of miR106‐5p, miR125b‐5p, and miR‐210‐3p, exhibited significant upregulation in NDE from probable dementia cases (p = 0.0128; p = 0.0011; p = 0.0030, respectively), interestingly, only males exhibited these results. Similarly, miR185‐5p, and miR342‐3p, associated with bIR, exhibited significant upregulation in NDE exclusively from male probable dementia cases (p<0.0001; p<0.0001, respectively). Furthermore, while miR‐16‐5p upregulation was exclusive to male probable dementia cases (p = 0.0070), miR‐138‐5p was the only investigated miRNA that exhibited downregulation and was unique to female probable dementia cases (p = 0.0063). Aβ40 expression positively correlated with miR‐185‐5p, miR‐125b‐5p, miR‐342‐3p, and miR‐210‐3p (p = 0.0331; p = 0.0188; p = 0.0001; p = 0.0052; respectively) and Aβ42 positively correlated with miR‐125b‐5p, miR‐342‐3p, and miR‐210‐3p (p = 0.0058; p = 0.0027; p = 0.0089; respectively). MMSE score was negatively correlated with miR‐185‐5p, miR‐342‐3p, and miR‐210‐3p (p<0.0001; p<0.0001; p = 0.0089; respectively). However, miR‐106b‐5p and miR‐125b‐5p were negatively correlated with MMSE score only in males (p = 0.0337; p = 0.0140; respectively). Conversely, only one miRNA, miR‐138‐5p, positively correlated with MMSE score and was exclusive to females (p = 0.0164).

Conclusion

This is the first study demonstrating the sex‐specific expression of AD‐ and bIR‐associated miRNAs in NDE, supporting the link between glucose metabolism dysregulation and the risk for dementia.
An innovative model using Promotores or Community Health Workers for home based dementia care
Authors: Patel Neela K. , Parker Cynthia De La Garza‐ , Davila Angelica , Garza Noe , Goss Monica , Satizabal Claudia L. , de Erausquin Gabriel A. , Maestre Gladys E. , Seshadri Sudha
Published: December 2023

Background

Health disparities and issues with trust building and relationship building are prominent in Hispanic and underserved populations in south Texas. Community health workers can play a bridging role with underserved communities and may be essential in improving the quality and value of health care. The Texas Health and Human Services Commission certifies the training Community Health Workers under the label of “promotores”.

Method

Community health workers were integrated into the primary health care team to serve as a bridge between patient/caregiver dyads and the health care team.

Result

Community health workers (CHWs) connected patients to social determinants of health resources such as transportation, food pantries and/or social benefits, Medicaid services, and home care provider services. Caregiver education and resources for respite care, caregiver support in person and virtually. Additionally, CHW’s provided education on dementia care resources, caregiver support, recruiting and engaging Hispanic underserve participants in research. Our team was able to increase home visits by 229% to homebound patients throughout several underserved zip codes in Bexar County. This is a success as our team was able to increase health care access to persons with dementia that are homebound that may have not been seen by a healthcare provider until they required emergency care. In fact, we saw roughly 11% decrease of inpatient admissions between 2021 and 2022.

Conclusion

Trust and familiarity allows the promotores to easily communicate interventions with cultural sensitivity and experiential knowledge of community values, leading to foster rapport with patients and families. The rapport and trust developed with the patients also helped to engage, and recruit Hispanic and underserved participants for research in dementia.