bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of a genetic risk score for Alzheimer’s disease on healthy elderly brain functional connectivity: A magnetoencephalography study
Authors: Rojo Inmaculada Concepción Rodríguez , Cuesta Pablo , Frutos Jaisalmer , Fernández Ricardo Bruña , García María Eugenia López , Calero Miguel , Ruiz Agustin , Moreno‐Grau Sonia , Toraño Federico Ramirez , Serrano Noelia , Sanz David López , Correas Ángeles , Higes Ramón López , Losada María Luisa Delgado , Dolado Alberto Marcos , Pereda Ernesto , Maestú Fernando , Fernández Alberto
Published: February 2022

Background

The study of the effects that certain genetic risk factors for Alzheimer’s disease (AD) has become a growing body of research. However, the relationship between brain integrity and performance and genetic profiles has been scarcely investigated. Here, we have calculated a genetic risk score (GRS), associated with an enhanced risk of developing AD. The GRS has been computed as the sum of the manifested risk alleles of 3 genetic polymorphisms for the CLU, PICALM and CR1 genes, each one weighted with the logarithm of its odds ratio. Additionally, we have carried out an eyes‐closed, resting‐state magnetoencephalography (MEG) study and analysed the brain functional connectivity (FC) of 230 cognitively intact elders non carriers of the APOE‐4 allele.

Method

230 healthy elders (aged from 61 to 85) were recruited from the Hospital Universitario San Carlos and the Center for elders at the Chamartín District, all located in Madrid, Spain. All of them underwent a neuropsychological evaluation, MRI assessment and MEG recordings.

Result

Beta band FC showed a selective vulnerability to the increased genetic risk that was captured by the GRS score. A clear pattern of hypersynchronization emerged in those participants with higher GRS scores.

Conclusion

GRS seems to be modulating electrophysiological brain activity inducing alterations in the beta band FC. To the best of our knowledge, this is the first MEG neuroimaging‐genetic approach within an elderly population that considers the possible association of a GRS for AD on brain neurophysiological activity.
Open science datasets from PREVENT‐AD, a longitudinal cohort of pre‐symptomatic Alzheimer’s disease
Authors: Tremblay‐Mercier Jennifer , Binette Alexa Pichet , Madjar Cécile , Remz Jordana , Das Samir , Evans Alan C. , Breitner John , Villeneuve Sylvia , Poirier Judes ,   PREVENT‐AD Research Group
Published: February 2022

Background

In the last 10 years, the PResymptomatic EValuation of Experimental or Novel Treatments for Alzheimer Disease (PREVENT‐AD) research program has collected both biological and behavioral data longitudinally, using well‐recognized biomarkers, to better understand and prevent Alzheimer’s disease (AD). Our cohort is composed of older individuals with a family history of AD, but who were themselves cognitively unimpaired when enrolled in the study (aged 63 years old ± 5, at entry). To move AD research further, we recently shared this rich dataset with the global research community.

Method

We created a data sharing model including two levels of access based on data sensitivity and risk of potential re‐identification, framed with a series of usage terms. Preparation of the datasets included selection of the variables to share, quality controls, outlier analysis, de‐identification, and creation of detailed data dictionaries for proper re‐usability. Each research participant was retrospectively re‐consented.

Result

More than 90% of participants (349 out of 386) agreed to openly share their data. Repositories are accessible openly at https://openpreventad.loris.ca, to qualified researchers at https://registeredpreventad.loris.ca, and through the unified interface of the Canadian Open Neuroscience Platform. The shared data collected from 2012 to 2020 (Table 1) includes longitudinal multimodal magnetic resonance imaging, gene variants, neuropsychological assessments, neurosensory evaluations, subjective cognitive decline information, as well as multiple behavioral data (e.g. sleep quality, neuropsychiatric factors, personality traits, etc). Amyloid and tau measurements from cerebrospinal fluid (n=106; longitudinal) and positron emission tomography (n = 130) are also available on subsamples of participants. To date, more than 250 users have accessed the PREVENT‐AD datasets.

Conclusion

Creation of open datasets from sensitive human data requires technical, human, and financial investments. The challenge remains important as we must constantly deploy our sharing initiative efforts as new data is collected, and new modalities incorporated in the cohort. By offering this evolving resource to the research community, we aim to acknowledge the implication of our research participants by expanding the potential of the data they generously provided, generate a higher rate of new discoveries in AD pathogenesis, and contribute to the international efforts towards prevention of AD.
Age effects on white matter microstructure in individuals of self‐identified Indian ancestry from the UK Biobank
Authors: Nabulsi Leila , Lawrence Katherine E. , Muir Alexandra M. , Santhalingam Vigneshwaran , Abaryan Zvart , Villalon‐Reina Julio E. , Nir Talia M. , Gari Iyad Ba , Zhu Alyssa H. , Haddad Elizabeth , John John P. , Venkatasubramanian Ganesan , Jahanshad Neda , Thompson Paul M.
Published: February 2022

Background

The incidence of dementia in India is 14%, and its prevalence doubles with every five‐year increase in age. Given the lack of ethnic diversity in most brain research to date, it is valuable to study cohorts with diverse genetic and environmental backgrounds, to identify predictors of health and disease that can be generalized to other ethnic groups than the commonly studied populations of European ancestry. To address this gap in the literature, we modeled factors that affect aging patterns in the brain’s white matter in individuals with Indian ancestry using advanced diffusion‐weighted MRI (dMRI).

Method

Cross‐sectional dMRI data from 123 individuals (males, n=78; females, n=45) of self‐reported Indian ancestry (born in India: 44%; mean age: 60.1±8.3 SD, range: 45‐80) from the UK Biobank were analyzed using diffusion tensor imaging (DTI), the tensor distribution function (TDF), neurite orientation dispersion and density imaging (NODDI) and mean apparent propagator MRI (MAPMRI). Main effects of age, sex, and age‐by‐sex interaction were investigated to characterize trajectories in whole‐brain white matter averages and the corpus callosum (CC), parcellated using the JHU‐ICBM atlas, covarying for years of education, waist/hip ratio, population structure (Figure 1) and the Townsend index. Normative lifespan charts were created to visualize white matter aging trajectories for the major diffusivity metrics.

Result

Normative centile curves (Figures 2‐3) show, with increasing age, declining white matter integrity, increased diffusivity, lower white matter density and diffusion restriction at the whole‐brain level and CC (Table 1; Figure 4). There was no detectable effect of sex, nor age‐by‐sex interaction, across whole‐brain metrics. In the CC, a steeper aging trajectory, evidenced by more pronounced white matter changes, was observed in males relative to females (Table 1; Figure 5).

Conclusion

Using advanced dMRI modeling, we report diffuse white matter changes with respect to age in a subsample of UK Biobank individuals of self‐reported Indian ancestry. Future studies should include larger sample sizes, comparisons with Indian ancestry individuals residing in India, consider vascular factors, and examine genotype interactions (e.g., with apolipoprotein E genotype), to further characterize risk factors and better understand brain aging in diverse populations with varied genetic and environmental backgrounds.
Co‐design of the DELIGHT (Dementia Lifestyle Interventions for Growing Healthy Together) program for persons living with dementia and care partners
Authors: Middleton Laura E , Keller Heather , McAiney Carrie A , Bechard Lauren Elizabeth , Wei Cindy , Koch Melissa , Heibein William , Roth Gail , Schneider Lloyd , Shoemaker David , Shoemaker Margaret ,   the DELIGHT Co‐design Team
Published: February 2022

Background

Persons living with dementia (PLWD) and family care partners (CPs) want to improve their health, maintain independence, and enhance well‐being. Multi‐domain interventions towards this goal are needed, but few are available and fewer were co‐created with PLWD, CPs, and program providers. The objective of the DELIGHT project is to use a participatory approach to co‐design a feasible, effective multi‐domain intervention (the DELIGHT program) that meets the health and well‐being goals of PLWD and CPs.

Method

Using a participatory approach, the DELIGHT project is guided by a core team of researchers, PLWD, CPs, and an Alzheimer Society representative. The co‐design team included the core team and additional PLWD/CPs, exercise professionals, dietitians, health care professionals, and community service providers (n=29). Due to COVID‐19, research team meetings have been virtual since May 2020. The co‐design was planned for four in‐person, half‐day sessions but was transitioned to six online, 1.5‐hour sessions, using small breakout rooms for discussion. The co‐design meetings focused on identifying target population, key outcomes of the program and developing program components and structure. During co‐design meetings, two or three guiding questions were set to focus discussion on a specific topic (e.g., exercise). The final co‐design session focused on the overall structure of the DELIGHT program. The core team then reflected on co‐design discussions and decisions and made final decisions on program structure. Program resources were iteratively designed with the core team, co‐design team, and other external stakeholders (including an illustrator).

Result

The DELIGHT program is designed to promote well‐being among PLWD and CP. Engagement soon after diagnosis is a goal. The program will meet twice per week for one hour of exercise and thirty minutes of facilitated discussion/education with a healthy snack and social engagement. Education will focus on healthy eating, sleeping well, mental well‐being, social connection, and physical activity. Program resources and manual are in development.

Conclusion

The DELIGHT program was co‐created by PLWD, CPs, researchers, and community stakeholders to meet the health and well‐being goals of PLWD and CPs. The on‐line and in‐person program options will be piloted and evaluated in fall 2021.
Using participatory research to co‐create the dementia‐inclusive choices for exercise toolkit
Authors: Middleton Laura E , Koch Melissa , Freeman Shannon , Pelletier Chelsea , Bechard Lauren Elizabeth , Mohamed Saara , Heibein William , Johannesson Carole , Dupuis Sherry L , Astell Arlene J. , Giangregorio Lora , Regan Kayla ,   the DICE Research Team
Published: February 2022

Background

Exercise improves functional abilities of persons living with dementia (PLWD) and provides an opportunity for social engagement, support, and inclusion. Yet, there are few exercise programs available to PLWD, especially in smaller communities. The goal of the Dementia‐Inclusive Choices for Exercise (DICE) project was to use participatory processes to create evidence‐informed knowledge translation (KT) resources to increase the number and quality of exercise opportunities for PLWD.

Method

The DICE core team includes PLWD, a family care partner (CP), exercise providers (EPs), dementia service providers (DSPs), health care professionals, and researchers. In the early project stages, we confirmed objectives and conducted 1 survey, 2 interviews, 16 focus groups to better understand barriers to and supports needed for exercise among PLWD. Results led to the prioritizing of primary (EPs) and secondary (PLWD & CP) target audiences for the KT resources. Co‐creation of the KT resources followed several steps: 1) drafting content and possible formats for resources over several core team meetings; 2) conducting a one‐day workshop with additional PLWD, CPs, EPs, and DSPs to develop a comprehensive plan for the content and format for each resource, target audience, and dissemination strategies; 3) using iterative design among the core team, resource developers, and additional PLWD, CPs, EPs, and DSPs to develop resources; and 4) usability testing.

Result

Key information to be translated included understanding the diversity of dementia, rights of PLWD to inclusion, physical activity guidelines/benefits, and dementia‐inclusive communication, practices, and design. This information is delivered through the DICE toolkit, which includes a website, on‐line training modules and manual targeted at exercise providers, destigmatizing videos that show the stories of PLWD, and resources for PLWD and their CPs to increase knowledge and confidence regarding exercise. Subsequent usability testing among EPs, PLWD, and CPs (n=7) identified design and content adjustments. Collaborative and inclusive decision making created improved relationships and ongoing learning between all stakeholders.

Conclusion

The participatory approach of the DICE project enabled stakeholders to identify and share perspectives and needs throughout the co‐creation process. Working collaboratively and iteratively with a diverse team ensured that the DICE toolkit is relevant and usable to EPs, PLWD, and CPs.
Cognitive impairment associated with global sensory processing abnormalities
Authors: Rhodus Elizabeth K , Barber Justin M , Gibson Allison , Thompson MaryEllen , Shady Kristine E , Jicha Gregory A
Published: February 2022

Background

Recognition of the impact of primary sensory impairment on cognitive status and decline in the aging population has spurred research in this area. Most prior studies have focused on primary sensory function, with few studying the potential impact of central nervous system sensory processing and modulation in relation to cognitive status.

Method

This study sought to evaluate sensory processing abnormalities rather than primary sensory deficits in community‐residing older adults through administration of the Adult Sensory Profile (ASP), a 60‐item, norm‐referenced assessment evaluating central nervous system sensory processing. The ASP items assess six sensory modalities: taste/smell, movement, visual, touch, auditory, and activity level. Participants ranked items based on their likelihood to engage in activities within each group. Responses were tabulated into four processing categories (sensation avoiding, sensory sensitivity, sensation seeking, and low registration) and compared with age‐cohort normative data. Identification of more than one category outside of normative results was indicative of sensory processing abnormalities compared to same‐aged peers. Participants were categorized based on the ASP as normal (<2 categories outside of normal range) or abnormal (2‐4 categories outside of normal range). Chi‐square tests compared cognitively normal participants to those with cognitive impairment.

Result

Seventeen participants completed the ASP. Eight were cognitively normal at the time of completion and nine were diagnosed with cognitive impairment. Of those with normal cognition, two were considered to have abnormal sensory processing (25%). Of those with cognitive impairment, seven were considered abnormal (78%), indicating a significant difference in global sensory processing between groups (x2=4.73, p=0.029).

Conclusion

Global sensory processing abnormalities were more frequent in those diagnosed with cognitive impairment compared to those that remained cognitively intact. It is likely that cortical neurodegeneration in sensory association areas is responsible for the increased prevalence of sensory processing abnormalities seen in the older adults with cognitive impairment in this study. Abnormal sensory processing abilities could contribute to increased behavioral and psychiatric symptoms, similar to that seen in children with severe sensory processing disorders. Larger studies are needed to confirm these results and investigate the relationship between impaired sensory processing and behavioral symptoms in dementia.
The normative data of cortical volumes in normal aging from Neuro I, a brain image quantitative analysis system
Authors: Choi Yu Yong , Hong Dongpyo , Park Jongseong , Heo Mina , Lim Da‐Hye , Seo Eun Hyun , Chung Ji Yeon , Chong Ari , Ha Jung‐Min , Choo Il Han , Kim Hoo Won , Lee Kun Ho , Hospital Chosun University
Published: February 2022

Background

The aging of brain is a topic has been constantly studied. Particularly, the norms for the elderly are important in diagnosing degenerative brain diseases, but the aging brain of East Asians has not been fully studied yet. “Neuro I” is a brain image quantitative analysis system with a built‐in large‐scale normative database for East Asians to provide quantified clinical information on how different an individual patient is from normal people. The study aimed to investigate ethnic differences of cortical brain volumes in normal elderly people, and to determine whether the norms considering racial disparities could improve the accuracy of diagnosis.

Method

Using Neuro I, cortical volumes were measured from brain magnetic resonance (MR) images of 1,686 cognitively normal elderly Koreans aged 59 to 89. For Caucasians, the brain images of 855 Caucasian‐Non‐Hispanic subjects were selected from the ADNI and OASIS datasets. The regression model predicting brain volumes were built using ethnicity, age, sex, intracranial volume (ICV), magnetic field strength (MFS), and scanner manufacturers as predictors. Based on the prediction model, the z‐scores of each individual were calculated. To validate the z‐score for diagnosis, 420 Alzheimer’s disease (AD) subjects of Koreans and Caucasians, and the same number of normal subjects were selected. The four validation groups divided by race and diagnosis were age‐ and sex‐matched using a propensity score matching method.

Result

The models predicting cortical volumes had a considerate amount of explained variance (mean R2: 55.8%, range: 42.7%–77.5%). Ethnicity explained substantial variances for temporal and parietal lobes (mean R2: 5.6%, range: 4.2%–7.5%), comparable to age (mean R2: 3.3%, range: 2.0%–4.3%). Furthermore, the z score of each region based on the model with ethnicity as a predictor (AUCs = .75, .72, .67, and .67 for left and right temporal and left and right parietal lobes, respectively) improved the accuracy of AD diagnosis compared to the z score based on the model without ethnicity (AUCs = .62, .59, .55, and .57).

Conclusion

Race or ethnicity should be considered for establishing the normative data in normal aging and AD diagnosis.
How much sleep is enough to avoid dementia or mild cognitive impairment? A systematic review and meta‐analysis of longitudinal studies
Authors: Tsoi Kelvin KF , Chan Joyce YC , Lee Helen WY , Bat Baker Kwok Kwan , Chan Tak Kit
Published: February 2022

Background

Dementia remains a global burden in aged populations and its contributing factors are still poorly known. While the lack of sleep has been proposed as a risk factor for dementia, evidence has emerged that excessive sleep might also be associated with increased risk for dementia. The present systematic review and meta‐analysis then aims to quantitatively clarify the correlation between dementia and sleep duration using a novel approach.

Method

Literature databases including PubMed and Embase were searched for studies reporting statistics on the proportion of participants with dementia or mild cognitive impairment (MCI) as well as the corresponding sleep duration. Unlike existing methods that measure odds ratios and relative ratios of developing dementia, the data were used to form a beta distribution that shows the likelihood of developing dementia / MCI given the sleep duration.

Result

The search identified a total of 6,522 articles, of these 10 studies involving 31510 participants in 7 countries were eligible for inclusion. The follow‐up time of these studies varied between 1 to 14 years. The relationship between dementia / MCI was U‐shaped. The distribution was asymmetrical with the implication that excessive sleep was associated with higher risk of dementia / MCI, compared with lack of sleep. In addition, higher risk of dementia rather than MCI was associated with sleep duration below 5 hours or above 9 hours.

Conclusion

The asymmetry of the distribution suggests the difference in the pathogenesis of dementia between the lack of sleep and excessive sleep. Coupled with existing findings that excessive sleep does not lead to the deposition of β‐amyloid, it is suggested that excessive sleep directly damages synapses in the absence of β‐amyloid accumulation. While there is still no plausible physiologic explanation for how excessive sleep and dementia is mediated, some have argued that excessive sleep could elevate the level of proinflammatory cytokine that has been suggested to reduce synapses.
A perspective from ethnomusicology: How to methodologically choose the correct music globally to awaken memories in the Alzheimer's patient
Authors: Pillay Jayendran
Published: February 2022

Background

Music tracks were assembled in sociocultural context and in autobiographical order as experienced by an Alzheimer's patient and tabularized with the patient's personal attendant emotions to each music track

Method

The patient and family members were interviewed, as per Ethnomusicological method, reconstructing the significant events in the patient's life, including the experience of any present music at that time. The music tracks were then played to the patient.

Result

The patient recalled many episodes of her life but lacked geographical and time perspectives such as when and where the events took place. Her posture and speech seemed to improve after she heard her familiar music. Her emotions mostly corresponded to how she felt earlier in life when first encountering the music.

Conclusion

Music potentially serves as a powerful trigger to awaken not just the memories associated with the music but others not associated with the music in a cascade effect. The patient had a better sense of her identity, while recalling the names of her family, some correctly and others not. The speech capacity was better after the patient's music was played as opposed to the interview phase done without music, suggesting that the music may trigger broader improvements beyond memory recollection. The emotions experienced via the triggered familiar music of significance were a strong driving force to recall specific events in her life. This pilot study needs to be expanded into different multicultural settings to ascertain its global impact.
Neuropsychological assessment of diverse populations in Europe: The European Consortium for Cross‐Cultural Neuropsychology (ECCroN)
Authors: Franzen Sanne , Mukadam Naaheed , Calia Clara , Watermeyer Tam J , Canevelli Marco , Pomati Simone , Goudsmit Miriam , van den Berg Esther , Papma Janne M , Ibanez‐Casas Inmaculada , Lozano‐Ruiz Alvaro , Fasfous Ahmed , Maillet Didier , Narme Pauline , Bekkhus‐Wetterberg Peter , Nielsen Rune
Published: February 2022

Background

Populations living in European countries are becoming increasingly diverse. As performance on traditional neuropsychological tests is heavily influenced by culture, language, (level and quality of) education, literacy, and other factors, neuropsychological assessment practices need to be adapted to account for this diversity.

Method

The European Consortium for Cross‐Cultural Neuropsychology (ECCroN) aims to improve assessment of culturally, educationally, and linguistically diverse individuals across Europe by 1) collaborating on the validation and implementation of cross‐cultural neuropsychological tests and 2) working on initiatives geared at improving interpreter use and training programs for neuropsychologists.

Result

The consortium was founded in late 2019 and currently consists of 16 experts based in 9 countries – some of whom work in multinational contexts. The first meetings of the network stressed several points. First, ECCroN aims to develop and/or validate cross‐culturally applicable tests, as opposed to race‐based norms for existing tests; for example, current projects aim to validate measures of social cognition and language (naming) in patients with migration backgrounds. Second, ECCroN emphasizes the importance of taking into account diversity across the entire spectrum, both in populations traditionally considered to be ‘majority’ and ‘minority’ groups, e.g. best practices should be developed for those with little education regardless of native‐born or migrant status. Third, ECCroN aims to identify and share suitable instruments to measure factors potentially influencing the assessment, such as bilingualism, acculturation and educational quality.

Conclusion

Joint efforts should be undertaken to develop, validate, publish, and implement cross‐cultural tests across European countries to reduce misdiagnoses in diverse patient populations.
A natural stimulus for entraining brain oscillations in Alzheimer's disease therapy: Canary song
Authors: Lahijanian Mojtaba , Alamalhoda Mohammad Amin , Aghajan Hamid
Published: February 2022

Background

The potential therapeutic effects of 40Hz gamma stimulation in Alzheimer's Disease (AD) has recently been under study (Suk et al. Alzheimer’s and Dementia 2020; Adaikkan et al., Trends in Neuroscience 2020; Sedghizadeh et al. Alzheimer’s and Dementia 2020). While measuring the gamma power as a marker for brain entrainment is well established in the literature, some studies have focused on theta‐gamma coupling (TGC) (Etter, Guillaume, et al., Nature Communications 2019; Munia & Aviyente, Scientific Reports 2019) as TGC is known to play a critical role in working/spatial memory tasks. Synthetic 40Hz amplitude‐modulated auditory chirp sounds have been used to entrain gamma oscillations. As a natural alternative, we propose the canary song, which is innate, pleasant, and includes diverse modulating sounds with chirp frequencies up to 20Hz. Since harmonic components are present in entrained response of the brain (Jones et al., Journal of Alzheimer's Disease 2019) albeit at lower powers, entrainment with the 20Hz canary chirp song can be a substitute for the commonly used synthetic 40Hz sounds.

Method

We observed the entrainment characteristics for the complete course of a canary’s singing as well as for selective 20Hz chirp segments of the song on eight young adults with simultaneous EEG recording. We measured the power spectrum and TGC strength during the stimulus and rest intervals on selective independent components (IC) of the recorded response.

Result

Canary song’s 20Hz chirp increases the theta band and 20Hz oscillation activity. During the stimuli intervals, ICs were found in the response close to the midbrain area that were entrained by the 20Hz stimuli while also showing high power in the theta band. TGC with high values around 40 Hz was also observed during the 20 Hz chirp intervals.

Conclusion

Employing natural sounds for AD therapy campaigns offers a more pleasant and serene alternative to artificial sounds. We selected segments of canary’s natural song which can produce entrainment effects similar to those of the synthetic 40Hz auditory tones commonly used for brain entrainment. Other natural sounds such as those of cricket and woodpecker can also be good candidates for entraining the brain in AD therapy.
Mathematical modeling reveals the correlates of cognitive impairment across the FTLD spectrum
Authors: Cividini Camilla , Agosta Federica , Basaia Silvia , Spinelli Edoardo Gioele , Castelnovo Veronica , Canu Elisa , Riva Nilo , Magnani Giuseppe , Caso Francesca , Filippi Massimo
Published: February 2022

Background

Amyotrophic lateral sclerosis (ALS), and behavioral variant frontotemporal dementia (bvFTD) lie on a continuum. The study aim was to apply mathematical modeling to unravel MRI connectomic signatures of cognitive/behavioral impairment in ALS.

Method

Eighty‐three ALS, 35 bvFTD and 61 controls underwent clinical/cognitive evaluations and MRI scan. Neuropsychological testing identified 54 ALS with only motor deficits (ALS‐motor), 21 ALS with cognitive/behavioral impairment (ALS‐ci/bi) and 8 ALS with bvFTD (ALS‐FTD). Structural and functional connectivity values were considered and normalized relative to controls. Statistical distribution analysis was performed between patient groups.

Result

Compared to ALS‐motor, bvFTD showed greater structural disruption within and between frontal, temporal and parietal lobes. Conversely, ALS‐motor showed a greater damage within sensorimotor–basal ganglia connections relative to bvFTD. ALS‐ci/bi and ALS‐FTD showed an ALS‐like pattern within motor areas, whereas a bvFTD‐like pattern was found only within the parietotemporal connections in ALS‐ci/bi and within frontal and frontal‐sensorimotor connections in ALS‐FTD. Functionally, bvFTD showed decreased functional connectivity in frontotemporal and sensorimotor‐parietal connections compared to ALS‐motor. ALS‐ci/bi showed enhanced functional connectivity relative to bvFTD in the frontal‐sensorimotor, parietotemporal connections and within sensorimotor areas, while ALS‐FTD showed reduced functional connectivity in temporal‐sensorimotor connections compared to ALS subgroups.

Conclusion

Two characteristic patterns were identified: alterations of the frontotemporal and parietal networks as bvFTD‐like, and a more focal damage within sensorimotor‐basal ganglia areas as ALS‐like, bringing to light features that ALS‐ci/bi and ALS‐FTD shared with the two ends of ALS‐bvFTD spectrum. The Italian Ministry of Health (GR‐2011‐02351217; GR‐2013‐02357415; RF‐2011‐02351193), AriSLA (ConnectALS), European Research Council (StG‐2016_714388_NeuroTRACK).
Impaired default mode network along with increased functional connectivity of the medial temporal lobe as a function of CSF p‐Tau/Ab42 ratio in cognitively unimpaired individuals
Authors: González‐de‐Echávarri José María , Milà‐Alomà Marta , Operto Greg , Falcon Carles , Minguillón Carolina , Fauria Karine , Simon Maryline , Kollmorgen Gwendlyn , Molinuevo Jose Luis , Zetterberg Henrik , Blennow Kaj , Suarez‐Calvet Marc , Gispert Juan Domingo , Cacciaglia Raffaele
Published: February 2022

Background

Amyloid‐b (Ab) and tau exert a synergistic action on brain structure and function in cognitively unimpaired (CU) individuals. However, these two biomarkers have so far been investigated separately. Recently, it was proposed that the cerebrospinal fluid (CSF) phospho‐tau (pTau)/Ab42 ratio may represent a novel prognostic core biomarker, providing information on both proteinopathies along the preclinical Alzheimer’s disease (AD) continuum. Here, we aim to characterize the association between CSF pTau/Ab42 and resting‐state functional connectivity (FC), an established imaging marker of AD, in CU individuals.

Method

We included 349 CU participants from the ALFA study (mean age=60.21 years) who underwent deep phenotype screening, including CSF data collection and resting‐state functional magnetic resonance imaging (fMRI). CSF Ab42 was assessed with the exploratory Roche NeuroToolKit arobust prototype assays, while pTau181 was measured with the Elecsys® Phospho‐Tau (181P) CSF immunoassay (Roche Diagnostics International Ltd). The CONN toolbox was used to preprocess and analyze the fMRI data. fMRI volumes were parceled into 218 regions and bivariate correlations in the filtered fMRI signal among parcels were computed. A linear regression model was used to assess the impact of continuous pTau/Ab42 ratio on FC, adjusting for age, sex, years of education and APOE‐e4 status. A threshold of uncorrected p<0.005 using non‐parametric pair‐wise clustering was implemented.

Result

Higher pTau/Ab42 ratio were associated with decreased FC within the default mode network (DMN) (Fig. 1), but increased FC within the temporo‐hippocampal (THN) and visual networks (VN) (Fig. 2). Also, we observed a reduced FC between the sensorimotor network and both the DMN and THN, as a function of pTau/Ab42 levels (Fig. 2).

Conclusion

Our results suggest that individuals with more advanced pathology in the preclinical AD continuum, reflected by higher pTau/Ab42 ratio, present altered FC across different distributed neural systems, both within and between networks. The reduced within‐DMN connectivity resembles earlier findings of DMN disruption as a function of cerebral Ab accumulation. However, the increased FC within the THN and VM may be indicative of a compensatory strategy to sustain cognitive functions despite AD pathology. Future studies shall include measures of cognitive performance along with longitudinal assessment to clarify this aspect.
Dilated brain perivascular spaces and their role in Alzheimer disease
Authors: Serra Guillermo Polanco , Liu Minghua , Guzman Vanessa A. , Rundek Tatjana , Kreisl William Charles , Gutierrez Jose
Published: February 2022

Background

Dilated small perivascular spaces (SPVS) have gained interest as MRI markers of cerebrovascular disease and possibly dementia.

Method

We leveraged existing data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to extract information regarding participants’ demographics, vascular risks, cognitive profile, APOE4 genotype and PET imaging for beta amyloid (AV‐45) and phospho tau (AV‐1451). For cognition and dementia status, we used the total Montreal Cognitive Assessment (MOCA), Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS‐Cog), and clinical dementia rating (CDR) scores. We used composite gray matter regions for PET measurements of amyloid and tau. We rated SPVS using a previously validated and reliable visual scale that assesses 14 brain regions for presence of SPVS. Each region was given a score of 0 (no SPVS), 1 (1‐3 SPVS), or 2(>3 SPVS). Regional scores were combined to create global SPVS scores. We built multivariate regression models using sex, age, education (in years), hypertension, prior stroke, white matter hypointensities (WMH) volume and APOE4 carrier status.

Result

We included 1,278 participants (mean age 75±8, 48%women, 89% non‐Hispanic white). SPVS were present in 85% of participants (median 6, range 0‐25). In multivariate analysis, SPVS score was associated with older age (B=0.05, P=0.01), history of stroke (B=6.9, P<0.001), WMH (B=0.33 per standard deviation, P=0.05) and marginally with hypertension (B=0.51, P=0.08). SPVS score, however, was associated with a higher MOCA score (B=0.06, P=0.03). There were no associations between SPVS with total ADAS score (B=‐0.02, P=0.71), CDR score (B= ‐0.03, P=0.07), amyloid (B=0.001, P=0.94) or tau (B=0.01, P=0.45).

Conclusion

Brain SPVS are associated with cerebrovascular disease and aging, but their additional value compared to other imaging markers of cerebrovascular disease as predictors of poorer cognition, dementia or Alzheimer disease is not supported by these data.
Association of lower heart rate variability with neuroimaging markers for dementia‐related pathology: The Multi‐Ethnic Study of Atherosclerosis (MESA)
Authors: Sandler Sebastian L. , Lockhart Samuel N. , Hiatt Kevin , Whitlow Christopher T. , Rapp Stephen R. , Sachs Bonnie C. , Soliman Elsayed Z. , Bertoni Alain , Heckbert Susan , Hughes Tim M. , Schaich Christopher L.
Published: February 2022

Background

Lower heart rate variability (HRV), indicating worse cardiac autonomic function, is associated with cardiovascular risk factors for dementia. We hypothesized that lower HRV would be associated with neuroimaging biomarkers for dementia‐related pathology independent of cardiovascular risk factors.

Method

During MESA Exam 6 (2016‐19), 256 white and African‐American Wake Forest site participants completed 3T brain MRI, and 159 further completed Aβ‐PET imaging. HRV was calculated as standard deviation of normal‐to‐normal intervals (SDNN) and root mean square of successive differences (RMSSD) from 10‐second electrocardiogram at Exam 1 (2000‐02) and Exam 5 (2010‐12). We related continuous (log2‐normalized) HRV to neuroimaging parameters including mean temporal lobe cortical thickness, neurite orientation dispersion and density imaging (NODDI) free water in gray (gmFW) and white matter (wmFW), and presence of cerebral microbleeds (CMBs), lacunes, and Aβ positivity (Pittsburgh Compound B SUVR ≥1.21) using multivariable linear and logistic regression, and examined race and sex interactions. To account for potential non‐linearity, we also considered the association of lowest quartile HRV to neuroimaging markers. Regression coefficients (β [95% CI]; standard deviation units) and odds ratios (OR [95% CI]) are adjusted for age, race, sex, education, systolic blood pressure, body mass index, smoking, hypertension medication use, diabetes, and APOE genotype.

Result

In 254 participants (Exam 6 age 72.2±6.9 years; 58.7% female; 47.2% white) with HRV measurements, lower continuous Exam 1 SDNN (β = ‐0.23 [‐0.39, ‐0.07]) and RMSSD (β = ‐0.19 [‐0.33, ‐0.05]) were associated with higher wmFW. Interactions showed that CMBs were associated with lowest quartile Exam 1 SDNN (OR = 3.76 [1.15, 12.25]) and Exam 5 RMSSD (OR = 3.36 [1.07, 10.54]) in males only (sex interaction P<0.001), and with Exam 1 SDNN (OR = 2.58 [1.04, 6.45]) in African‐Americans only (race interaction P = 0.039). Lower HRV was not associated with cortical thickness or presence of lacunes. In 152 participants with Aβ‐PET, no associations with Aβ deposition were found.

Conclusion

Lower HRV from up to 16 years prior may be associated with increased neuroinflammation as measured by free water in older adults. Associations between HRV and cerebral small vessel disease markers may differ by sex or race.
Old critically ill COVID‐19 survivors: Patient and in‐hospital factors associated with cognitive dysfunction
Authors: Martins Sónia , Ferreira Ana Rita , Fernandes Joana , Vieira Tatiana , Fontes Liliana , Coimbra Isabel , Paiva José Artur , Fernandes Lia
Published: February 2022

Background

Cognitive dysfunction (CD) commonly occurs in survivors of critical illness, namely in those with severe respiratory failure, invasive mechanical ventilation (IMV), deep sedation and delirium. Many critically ill patients with COVID‐19 are also expected to have an increased risk of CD, which may be exacerbated by specific conditions of hospitalization during COVID‐19 pandemic. This study aimed to estimate the frequency of post‐discharge CD in first wave COVID‐19 survivors and to identify baseline and in‐hospital associated factors.

Methods

This study is part of a multidisciplinary longitudinal project (MAPA‐Mental health in critically ill COVID‐19 patients), that is being conducted in Intensive Care Medicine Department of a Portuguese University Hospital. Patients >60 years, admitted due to COVID‐19‐associated Pneumonia, were included. Exclusion criteria were: Intensive Care Unit (ICU) length of stay (LoS)≤24h, terminal illness, major sensory loss or inability to communicate at the time of follow‐up. Participants were evaluated with Six‐item Cognitive Impairment Test (6CIT) by telephone. Baseline demographic, clinical and in‐hospital data were collected, including sedation, respiratory support, major complications and LoS. Patients with and without CD after‐discharge were compared.

Results

Thirty‐two patients were included, with a median age of 72(IQR:64‐76) years, mostly were male (66%) and none had previous clinical registry of cognitive impairment or dementia. Nosocomial infection (75%) and difficult weaning from MV (63%) were the most frequent complications. Deep sedation was used in 81% of the patients (median=20 days; IQR:15‐42). About 81% needed IMV and 13% were supported with Extracorporeal Membrane Oxygenation (ECMO). Median ICU and hospital LoS were 29(IQR:144‐56) and 66(IQR:33‐102) days, respectively. Follow‐up assessment occurred 93.4 days (IQR:68‐120) after‐discharge. Based on 6CIT, 16% of survivors had CD. Comparing both groups, those with CD were older (73vs.64; p=0.020), had a higher duration of IMV (73vs.22; p=0.017) and mostly were supported with ECMO (75%vs.25%; p=0.008).

Conclusion

Data suggest that CD is more frequent among older COVID‐19 survivors, and those who needed prolonged IMV and ECMO support. Despite full clarification of all mechanisms involved, these findings highlight the importance of a timely and organized post‐intensive care response composed by multidisciplinary teams to optimize assistance to survivors of critical illness.
APOE‐ε4 status moderates the relationship between body mass index and hippocampal structure in older African Americans
Authors: Fausto Bernadette A. , Osiecka Zuzanna , Gluck Mark A.
Published: February 2022

Background

Growing evidence suggests that traditional body mass index (BMI) cutoff values may overestimate adiposity and its health consequences in African Americans. Further, while obesity disproportionately affects African Americans, obesity is inconsistently associated with Alzheimer’s disease (AD) in older adulthood. Examining the influence of BMI and its interaction with the strongest genetic risk factor of AD, the APOE‐ε4 allele, on hippocampal‐dependent cognitive performance and medial temporal lobe (MTL) structure may provide insights into the complex relationship between obesity and AD in older African Americans.

Method

Analyses included 70 cognitively normal older African Americans (mean age=69.50 years, SD=7.18; mean education=14.12 years, SD
2; 38.60% APOE‐4 allele carriers) who completed cognitive testing, saliva sampling for APOE genotyping, and structural neuroimaging to extract MTL cortical region/hippocampal subfield volumes and surface areas. Cognitive tests included the following measures of generalization and episodic memory: Concurrent Discrimination and Transfer Task, Acquired Equivalence Task, and Rey Auditory Verbal Learning Test. ANCOVAs were used to compare BMI groups (normal: 18‐24.9 kg/m2; overweight: 25‐29.9 kg/m2; class 1 obesity: 30‐34.9 kg/m22) and to test for BMIxAPOE interactions on cognitive and neuroimaging outcomes, while controlling for age, sex, education, literacy, and depressive symptomology.

Result

There was a statistically significant difference between BMI groups on Concurrent Discrimination and Transfer Task performance, p=.01, partial η
2=.18. The normal and class 2 obesity group committed significantly greater errors than either the overweight or class 1 obesity group, ps < .05. Significant BMIxAPOE interactions were identified for the following hippocampal subfield volumes and surface areas: left DG/CA3 and left CA1, ps < .05. For APOE‐ε4 non‐carriers, the normal BMI group had significantly smaller left DG/CA3 and CA1 subfields than the other groups. Among APOE‐ε4 carriers, the class 2 obesity group had smaller left DG/CA3 and CA1 subfields than the other groups.

Conclusion

Being overweight may confer cognitive protection in older African Americans. However, obesity appears to be selectively detrimental to hippocampal subfield structure among APOE‐ε4 carriers while normal BMI may be deleterious to hippocampal subfield structure among APOE‐ε4 non‐carriers.
Characterizing communication in dementia family caregiving: Identifying breakdown and repairs using the trouble source repair (TSR) framework via video observations
Authors: Coleman Carissa K , Williams Kristine N , Berkley Amy , Dunham Ashlyn , Savundranayagam Marie Y
Published: February 2022

Background

Families who provide care at home for people living with dementia (PLWD) are an integral part of dementia care worldwide and improving in‐home care is crucial. Communication is fundamental for daily care and communication breakdown presents additional stress to the caregiver‐PLWD dyad. In order to identify effective strategies that will minimize communication breakdown, we adapted the Trouble Source Repair (TSR) framework, a linguistic tool, to create a second‐by‐second behavioral coding scheme for video observations. This pilot study used the adapted TSR coding scheme to reliability identify communication breakdown and repair.

Method

This pilot study analyzed videos from a randomized controlled trial of a family caregiver telehealth intervention (FamTechCare). The videos were created by caregivers in their home, providing observations of natural caregiver‐PLWD interactions across a variety of daily care activities. Operational definitions from the TSR were adapted to create a coding scheme (Table 1). Video data collection and analysis were completed using Noldus software. Two independent coders obtained reliability.

Result

The video sample includes 51 dyads with 201 videos averaging 5.8 minutes in length. Caregivers were primarily female (80%), mean age 65 years, and were mostly a spouse (69%) while the PLWDs were primarily male (55%) with moderate to severe dementia (64.7%). The mean interrater reliability was excellent; Kappa = .93. Preliminary descriptive results (n=106) indicate 53.7% of the dyad communication was interactive, 8% was communication breakdown, and the remainder was silence or talking to others. During a typical breakdown sequence, the caregiver’s communication creates the breakdown (Trouble Source, 67%), the PLWD indicates not understanding (Flag, 71%) and the caregiver initiates the Repair (72%). Breakdowns were successfully resolved 71% of the time. Types of trouble sources, flags, and repairs can be seen in Table 2.

Conclusion

The results support the use of the adapted TSR framework to reliability identify communication breakdowns via video observation. Future analyses will identify the most effective strategies to prevent and repair communication breakdown as well identify how strategies varies by dementia stage, diagnosis, and dyad characteristics.
Improvement in distinct cognitive functions between tablet PC and workbook in the SUPERBRAIN study
Authors: Park Hee Kyung , Na Hae Ri , Jeong Jee Hyang , Moon So Young , Hong Chang Hyung , Park Yoo Kyoung
Published: February 2022

Background

We aimed to compare the effect in cognition according to the type of cognitive training in the SUPERBRAIN study, a 24‐week multi‐domain lifestyle intervention program to prevent dementia.

Method

Both cognitive training programs, targeting five or six cognitive domains, were conducted in a group session or individually at home. The primary outcome was the change in the total scale of index score of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) after 6 months of training. Analysis of covariance was used to compare the index score of the RBANS between the three groups.

Result

There were significant improvements in the total scale index score (adjusted mean of change of the score, standard error; 6.2, 1.3; controls, ‐1.3, 1.6; p <0.001), attention (2.0, 1.3; controls, ‐2.0, 1.7; p=0.020), and delayed memory (9.9, 1.3; controls, 4.9. 1.8; p=0.014) in the tablet PC group compared to control group. The degree of improvement in immediate memory (6.4, 1.5; p=0.029) was larger in tablet PC group compared to the workbook group (0.1, 2.1). Improvement in visuoconstruction (1.2, 2.5; controls, ‐9.4, 2.3; p=0.002) was shown in the workbook group compared to the control group.

Conclusion

The degree of improvement in total scale index score of the RBANS, immediate and delayed memory, and attention was more pronounced in the tablet PC group compared to the control group or workbook group. The workbook group displayed a larger degree of improvement in visuoconstruction compared to the control group. These findings implicate that cognition can be improved through cognitive training programs in at‐risk population and cognitive training programs using tablet PC or workbook seem to show improvement in different cognitive functions.