bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of biomarkers in cell counting with U‐Net CNN
Authors: Miramontes Silvia , Piergies Antonia M.H. , Grinberg Lea T. , Ushizima Daniela
Published: February 2022

Background

Imaging methods that are non‐destructive preserve tissue integrity and lead to improved topography analysis for the study of neurodegenerative diseases like Alzheimer’s Disease (AD). Immunofluorescence (IF) staining methods facilitate such investigations by addressing a gradient of intensity variations relevant for in situ cell detection [1] and morphology quantification. This paper reports on the colocalization of proteins and cell structures from human post‐mortem tissue by evaluating IF expression by means of TBR1 and NeuN biomarkers. We compare different U‐Net‐based models by exploring image representations obtained by combining image channels with different biomarkers.

Method

From an image dataset with 21 full‐size IF micrographs, we perform data augmentation by creating a cropping mechanism resulting in 40 to 60 image crops from each micrograph, each crop with 128x128 pixels. Later, we enhance the resulting 1,200 cropped images, and construct 3‐channel (X,Y,Z) image inputs of dimensions 128x128x3 for the U‐Net model in a two‐fold process: (I) stack all 3 channels with single‐channel IF cropped images corresponding to NeuN biomarkers (NeuN, NeuN, NeuN); (II) stack the single channel images of TBR1, NeuN, and a single image representing the maximum pixel intensities from TBR1 and NeuN images (TBR1, NeuN, max (TBR1, NeuN)). With a test‐train split of 70% ‐ 30%, and parameter tuning, we compare the two models via metrics such as neuron areas, counts, accuracy and recall.

Result

The model trained with channel stacking (II) outperforms the model trained with (I) with an accuracy and recall of 0.96 and 0.5, as opposed to 0.95 and 0.4. We also found a great variation in neuron area and counts as depicted in the images below.

Conclusion

While this is the first step in accelerating the quantification of neurons for the pathophysiology studies necessary for drug development, there is a need in establishing protocols for the generation of datasets with manual segmentation to further train our models. The inclusion of prior information about the expected neuron morphology increases the performance of our networks, and can successfully deploy a foreseen automated pipeline. [1] Ehrenberg et al. A manual multiplex immunofluorescence method for investigating neurodegenerative diseases. Journal of Neuroscience Methods,June, 2020.
Initial biological evaluations of a novel microtubule‐based PET ligand in Alzheimer’s disease
Authors: Damuka Naresh , Orr Miranda E. , Macauley Shannon L. , Shively Carol A. , Lockhart Samuel N. , Bansode Avinash , Kim Jeongchul , Frye Brett M. , Register Thomas C. , Mintz Akiva , Whitlow Christopher T. , Craft Suzanne , Solingapuram Sai Kiran K.
Published: February 2022

Background

Microtubule (MT) integrity is critical for cell function and viability. Abnormal MT‐stability in AD is commonly attributed to hyperphosphorylation of the MT‐associated protein, tau. However, the time course of MT instability in disease progression remains unknown. In vivo MT imaging offers an opportunity to gain critical information on MT changes in relation to staging of ADRDs. Our lab reported the first brain‐penetrant MT PET ligand, [11C]MPC‐6827 and evaluated in vivo imaging in normal rodents and non‐human primates (NHP). Herein we report its initial biological evaluations in (a) neuronal cells, (b) tau knock‐out mice, and (c) aged NHPs (Caribbean‐origin vervets) with changes in AD‐related biomarkers.

Method

In vitro [11C]MPC‐6827 cell uptake assay was performed in patient‐derived SH‐SY5Y cells with different MT destabilizing and stabilizing agents. Radioactive binding efficiency was determined as %ID (injected dose)/mg of protein present in each well. Dynamic 0‐60 min brain microPET/CT imaging was performed in tau knock‐out and wild type mice (n=4). Four vervets (20‐29y) with different cerebrospinal fluid (CSF) Aβ42 levels (2 high levels‐1461, 1614 and 2 low levels‐579,732) underwent 0‐120 min brain PET/CT imaging with [11C]MPC‐6827. ROIs were drawn on the whole‐brain and SUVR values were calculated from co‐registered PET/MR images.

Result

In vitro cell uptake assays with [11C]MPC‐6827 in SH‐SY5Y cells displayed high uptake with MT destabilizing agents and low uptake with stabilizing agents. MicroPET imaging demonstrated higher radioactive brain uptake in tau knockout over wild‐type mice. Vervets with low CSF Aβ42 levels showed high radioactive brain uptake and the youngest vervet (20y) displayed lowest brain uptake.

Conclusion

Consistent with our in vitro cell uptake and in vivo rodent imaging experiments, [11C]MPC‐6827 increased with MT destabilizations. Radioactive uptake was inversely related to CSF Aβ levels and directly related to age in a NHP model of AD (Fig 1). Collectively our data suggest that [11C]MPC‐6827 is more selective towards destabilized MTs. On‐going experiments include rigorous PET imaging analyses, determination of metabolic plasma‐blood parameters, and correlations with Aβ42 and tau levels. Nonetheless, our promising results support the high translational utility of [11C]MPC‐6827 to image MTs in ADRDs.
Understanding proxy decision‐makers’ perspectives of frailty and frailty tools to support decision‐making for persons with dementia
Authors: Shapkin KImberly , Bent Haley , Callaway Lorna , Cooper Mary Elizabeth , Randhawa Sukhjeet Kaur , Murphy Angela , Lazar Faye , Cuthbert Colleen
Published: February 2022

Background

Proxy decision‐makers’ for persons with dementia (PwD) have identified feeling uninformed about the prognosis and progression of dementia and unsupported by healthcare professionals. One aim of our study was to explore how frailty is understood and if frailty tools may assist with decision‐making.

Method

We conducted a qualitative inquiry using focus groups to explore decision‐makers understanding of frailty and their perspectives of using frailty tools. Proxy decision‐makers were identified as formal agents of a PwD. Focus groups were recorded and transcribed verbatim. Data was analyzed and interpreted using thematic analysis.

Result

Analysis revealed the prevailing theme to be, frailty is understood as a mosaic. Decision‐makers’ primarily consider frailty a physical phenomenon, closely paralleling Fried’s (2000) frailty phenotype: weight loss, low activity, slow gait, weakness and fatigue. Participants also associated frailty with cognitive decline and emotional instability. Applying the term frailty to PwD produced an ambivalent response in participants, although the term itself was considered as acceptable to describe physical decline. Participants valued the Clinical Frailty Scale to aid in the understanding of the progression of physical decline, but felt the limited recognition of cognitive decline was a barrier. The fluctuating course of dementia also limited the utility of using a tool with fixed categories.

Conclusion

Frailty is a recognizable term to proxy decision‐makers, but is understood in a variety of ways, primarily as a physical phenomenon. Given the ambivalence in using this term and decision‐makers’ focus on cognitive changes, discussing frailty has little to add to improve supporting decision‐making in dementia.
Apolipoprotein ε genotype modifies the association between blood‐brain barrier permeability and both grey and white matter integrity in older adults
Authors: Schimmel Samantha J. , Shashikumar Niranjana , Pechman Kimberly R. , Gifford Katherine A. , Landman Bennett A. , Blennow Kaj , Zetterberg Henrik , Hohman Timothy J. , Jefferson Angela L. , Moore Elizabeth E.
Published: February 2022

Background

Blood‐brain barrier (BBB) permeability has been implicated in Alzheimer’s disease and is associated with decreased cerebral blood flow and cognitive impairment. However, associations between BBB permeability and structural brain changes remain unknown. This study relates the cerebrospinal fluid (CSF)/plasma albumin ratio, a proxy measure for BBB permeability, to grey matter volumes and white matter integrity

Method

Vanderbilt Memory and Aging Project participants free of clinical dementia or stroke (n=148, 72±6 years, 41% female, 32% apolipoprotein E (APOE) ε4 positive) underwent fasting lumbar puncture for CSF sampling and blood draw for plasma sampling. Participants underwent 3T T1‐weighted imaging to quantify grey matter volumes and diffusion tensor imaging (DTI) to quantify white matter integrity. Voxel‐wise analyses using non‐parametric permutations cross‐sectionally related the CSF/plasma albumin ratio to DTI metrics, adjusting for demographic and health variables, diagnosis, and APOE‐ε4 status. Linear regressions related the CSF/plasma albumin ratio to grey matter volumes, adjusting for identical covariates plus intracranial volume. Follow‐up models tested interactions with APOE‐ε4 status.

Result

In the entire sample, the CSF/plasma albumin ratio was unrelated to grey matter volumes and white matter integrity (p‐values>0.28) but interacted with APOE‐ε4 status on total grey matter (p‐value=0.02), frontal lobe (p‐value=0.01), and occipital lobe volumes (p‐value=0.04). Stratification suggested a higher CSF/plasma albumin ratio, indicating impaired BBB function, related to smaller grey matter volumes among APOE‐ε4 carriers. The CSF/plasma albumin ratio also interacted with APOE‐ε4 status on white matter integrity in the temporal and frontal lobes (p‐values<0.05), with associations present in APOE‐ε4 non‐carriers.

Conclusion

Increased BBB permeability is associated with decreased grey matter volume in APOE‐ε4 carriers, specifically in the frontal and occipital lobes. APOE‐ε4 may act as a vascular modifier in these regions, such that increased BBB permeability exacerbates underlying neurotoxicity and neurodegeneration. In contrast, the association between increased BBB permeability and compromised white matter integrity is driven by APOE‐ε4 non‐carriers. Taken together, these results suggest that BBB permeability may be an etiology of neurodegeneration in APOE‐ε4 carriers and highlight the importance of APOE‐ε4 status when studying BBB effects on brain health.
Spousal dementia caregivers' use of technology during the COVID‐19 global pandemic: Lessons learned from the NYU family support program
Authors: O'Connor Maureen K , Donley Tiffany , Salant Rebecca , Nicholson Roscoe , Epstein Cynthia , Nguyen Andrew Huy , Stevenson Elizabeth , Shirk Steven , Mittelman Mary S
Published: February 2022

Background

Daily routines have been drastically impacted by COVID‐19, including healthcare appointments, home services, and many recreational opportunities. Spousal dementia caregivers (CGs) are particularly vulnerable during COVID‐19, as many rely on family members, daycare, in‐home assistance, and other respite opportunities. We conducted qualitative interviews in May/June 2020 to understand the impact of COVID‐19 on dementia CGs and how they experienced the switch of all the NYU ADRD Family Support Program (FSP) services to telehealth.

Method

A total of 10 spousal CGs participated in videoconference interviews about their COVID‐19 experiences and the FSP’s transition to the telehealth format. Semi‐structured interviews were conducted by one of two interviewers who were external to the FSP to encourage freedom of discussion. All sessions were recorded and transcribed. De‐identified transcripts were coded by two independent coders using NVivo, with discrepancies resolved by a third researcher.

Result

CGs ranged in age from 54 to 86; 7 were female, 8 were non‐Hispanic White, and 2 were Black. All were New York City residents living with the person with dementia; 2 households had additional adult family members. Qualitative analysis revealed several major themes related to COVID‐19 experiences: fears surrounding COVID‐19 and staying healthy; changes in daily routines; the impact of reduced respite and support services; adaptation to technology that enabled increased contact with family/friends. Feedback about the telehealth adaptation of the FSP included observations about new group dynamics and decreased barriers to involvement due to the ability to participate from home, reducing the need for transportation and other logistics related to traveling.

Conclusion

Despite significant challenges due to COVID‐19, CGs reported benefit and support from the FSP in the new telehealth format. One participant described the FSP as “indispensable” and expressed how much members relied on each other during COVID‐19. In addition, we learned that the telehealth FSP not only served as a source of support during the crisis but that there were perceived advantages to this format, including reductions in barriers to in‐person services (finding transportation, travel time, getting respite care for the person with dementia). We recommend continuing the option of telehealth services for dementia CGs after the COVID‐19 crisis.
Socio‐psychological impact of COVID‐19 on a diverse cohort of older adult research participants in New York
Authors: Loizos Maria , Sewell Margaret , Neugroschl Judith A , Zhu Carolyn W , Li Clara , Zeng Xiaoyi , Pun Kelly , Velasco Nelly , Tocco Carly , Sheppard Faye , Ardolino Allison , Meuser Caroline , Greenberg Jonathan , Evans Kirsten , Kinsella Michael T , Aloysi Amy , Grossman Hillel , Sano Mary
Published: February 2022

Background

During the spring of 2020, New York was overwhelmed by COVID‐19 and older adults as well as ethnic minorities were disproportionately affected. The Alzheimer’s Disease Research Center (ADRC) located in East Harlem in New York City, serves a predominantly low income, Latinx community. It was imperative to gauge the impact of COVID‐19 on our diverse group of older adult research participants.

Method

Participants enrolled in the ADRC with a Clinical Dementia Rating Scale of 0 (75%) or .5 (24%) completed evaluations between May and December 2020 for the National Alzheimer’s Cooperative Center Uniform Data Set (NACC UDS) and were administered a 33‐item COVID‐19 questionnaire over the telephone that was modified from the questionnaire provided by NACC. The 15–20 minute survey asked questions about social, psychological, and emotional experiences with COVID‐19, including whether they had lost a loved one to COVID, as well as items targeting the psychological sequelae of the pandemic (depression, isolation, a sense of loss of control, for example).

Result

198 participants completed the questionnaire. Of these, 55% were non‐Hispanic White, 15% were non‐Hispanic Black, 14% were Hispanic, and 16% were Asian. The overall sample’s mean age was 76.4±7.5, mean education 15.80±3.1years, and 62.6% were male. Survey results indicated that 89% felt the pandemic had been disruptive to their lives, and 30% had lost a loved one to COVID. Sixty‐three percent of participants reported being in touch remotely with friends or family nearly every day, and 24% 2‐3x/week. Thirty two percent reported feeling they could not control important things in their life and feeling anxious (46%), bored (41%), and lonely (30%). Twenty seven percent reported feeling depressed and 23% experienced sleep problems.

Conclusion

In this diverse sample of community dwelling older adults, most were able to remain in close contact with family and friends, and many reported the pandemic as disruptive. However, fewer reported experiencing a loss of control as well as psychological or emotional distress (i.e., depression) which may reflect adaptive mechanisms worthy of further study.
Visual entrainment responses are altered in patients with mild cognitive impairment and Alzheimer’s disease
Authors: Springer Seth D. , Wiesman Alex I. , May Pamela E. , Schantell Mikki D. , Christopher‐Hayes Nicholas , Johnson Hallie J. , Willet Madelyn P. , Eastman Jacob A. , Wolfson Sara L. , Johnson Craig M. , Murman Daniel L. , Wilson Tony W.
Published: February 2022

Background

Alzheimer’s disease (AD) is the most common cause of dementia in later life. AD is histologically characterized by the accumulation of extracellular amyloid‐β (Aβ) plaques and intracellular hyperphosphorylated‐tau neurofibrillary tangles. Recent research has indicated that visual entrainment may be useful in clearing Aβ‐ and tau‐load in the central nervous system in mouse models of AD. However, human studies in this area are rare and the degree to which patients with AD exhibit aberrations in visual entrainment are unknown, as is the impact of entrainment on amyloid and tau‐load.

Method

We recorded magnetoencephalography (MEG) during a 15‐Hz visual entrainment paradigm in amyloid‐positive patients on the AD spectrum and compared their neural responses to biomarker‐negative, demographically‐matched, cognitively‐normal controls. MEG data were imaged using a beamformer and virtual sensor data were extracted from the peak responses.

Result

Our results indicated that participants on the AD spectrum exhibited significantly stronger entrainment relative to baseline in primary visual cortices. However, interestingly, the two groups exhibited roughly equal absolute levels of entrainment, which suggests lower spontaneous levels of 15‐Hz activity in the AD spectrum group. Additionally, we found that higher absolute levels of entertainment predicted greater MoCA scores.

Conclusion

This pattern of results indicates that the increased entrainment in patients on the AD spectrum was compensatory and that those patients who were closer to the level seen in controls had better cognitive performance. Overall, these results indicate that entrainment may be altered in humans with AD and should be further examined in future studies.
Exploring older adults' experiences using technology during a viral pandemic
Authors: Barber Justin M , Scherer Sally , Rhodus Elizabeth K , Kelly Parsons R , Johnson Julia , Hall Megan , Snyder Katherine , Coy Beth , Boggess Bailee , Lowry Kimberly , Shaffer Andrea , McRoberts Tyler , Jicha Gregory A , Gibson Allison , Bardach Shoshana H
Published: February 2022

Background

Older adults are at greater risk for morbidity and mortality associated with COVID‐19. Spatial distancing and sequestering practices are recommended to limit viral exposure. Older adults adopting these practices are at increased risk of social isolation and adverse health outcomes. Remote technologies offer various platforms for satisfying socialization and healthcare needs while sequestering. Understanding how older adults are using technology has implications for wellbeing during a pandemic.

Method

Researchers attempted to contact all participants enrolled in the University of Kentucky Alzheimer's Disease Research Center longitudinal study via telephone to survey technology use (n = 706). Participants were contacted directly, except for demented participants, whose primary caregivers were contacted to respond on their behalf, when possible. Participants and caregivers gave their assent verbally to complete the voluntary survey, the procedures of which were approved by the IRB. The surveys consisted of validated instruments to gauge the extent of use of and comfort with technology. Spearman correlations, chi‐square tests, and t‐tests were used to explore data.

Result

Ultimately, 384 participants were reached and 332 consented to participate. Most reported reliable home internet access (91.5%) and some internet use (90.6%). Recent feelings of loneliness were not related to any technology‐related variables (all ps > 0.29) other than decreasing with greater willingness to use telehealth (Rho = ‐0.11, p = 0.06). Those who reported a lack of comfort with technology (n = 76) were less likely to text messaging (67% vs 78%) and social media (56% vs 69%), ps ≤ 0.06, but felt socially connected using technology at similar levels (82% vs 75%), p = 0.22. Nearly 70% of this group reported they would use technology more with training. Across all participants, willingness to use telehealth was not related to frequency of frustration with tech (Rho = 0, p = 0.99).

Conclusion

The results suggest that some older adults’ use of technology is limited by familiarity. Lack of familiarity does not appear to create a barrier to using telehealth nor does frustration with technology appear to limit telehealth use. The findings have implications for supporting older adults sequestered during a pandemic but potentially more broadly.
Frailty syndrome in early‐onset autosomal dominant Alzheimer disease, in the PSEN1‐E280A kindred
Authors: Garcia‐Cifuentes Elkin , Aguillon David , Velez Juan Esteban , Gómez Manuela , Gómez‐Henck Clara , Deossa‐Restrepo Gloria , Saldarriaga Jonathan , Jaramillo‐Jimenez Alberto , Ciro Jorge Alberto Osorio , Borda Miguel German , Cano‐Gutierrez Carlos Alberto , Lopera Francisco
Published: February 2022

Background

Dementia has become a healthcare priority. As no disease‐modifying treatment is available, treatment is aimed to act through prevention. Frailty have been defined as a geriatric multidimensional syndrome. Being a treatable condition, interest has raised to describe the relationship between Dementia and Frailty. This study describes frailty in the Autosomal Dominant Alzheimer Disease, through the largest ADAD known group.

Method

A total of 75 participants (14 with MCI and 61 with Dementia) were included in this cross sectional study. They underwent a complete assessment that included a standardized clinical examination, neuropsychological evaluation and functional scales. Frailty was assessed through the Short Physical Performance Battery (SPPB) and the Time up and Go Test (TUG) . Multivariate analyses was conducted to evaluate which variables were associated with being frail in presenile onset of ADAD.

Result

In the 75 patients who underwent the study, median age was of 49 years old with a cognitive profile of 18.67 % individuals with MCI, 21 % with Mild, 28 % with Moderate and 25 % Severe Dementia. According to the frailty phenotype: 60 % were non‐frail and 40 % frail. When analyzing, SPPB and TUG components: Median Gait Speed in MCI and mild dementia groups were statistically significantly lower than moderate and severe dementia (p< 0.005) and significantly greater TUG was found in moderate and severe dementia groups when compared with MCI and mild dementia(p<0.005) Both, clinical severity grouped in moderate – severe dementia (OR 6.85; CI 2.07‐22.65 p< 0.000) and hypertension (OR 5.80; CI1.56‐21.49 <0.002) are significantly associated with being frail.

Conclusion

This study is the first description of frailty syndrome in ADAD with a presenile onset. The prevalence found in this population is similar than in previous reports in older adults and thus reasserts the adaptability of frailty evaluation in young patients with special clinical conditions. Our data supports the existing relationship between frailty and dementia. As the cause of dementia in our patients is purely genetic, effects of aging are controlled and excluded. This enrich science and lights up the search of new mechanisms linking both conditions.
The dementia journey survey: A community engagement approach for inclusivity in dementia care research
Authors: Iroanyah Ngozi Faith
Published: February 2022

Background

Approximately 560,000 people live with dementia (PLWD) in Canada, yet research on the experiences of ethnoculturally diverse people with dementia is largely unknown. As a result, healthcare programs and services do not reflect the dementia related needs of these communities. Additionally, 60% of primary care physicians indicated feeling uncomfortable supporting patients with dementia, despite being the first point of access for additional dementia healthcare. To address these gaps, a national collaboration was developed by the Alzheimer Society of Canada (ASC) and the College of Family Physicians of Canada (CFPC) to understand more diverse experiences of PLWD with their healthcare providers.

Method

Using a mixed methods design, paper and online surveys were created for PLWD and caregivers, and online surveys were created for family physicians. CFPC registered family physicians were invited to participate through professional channels. PLWD, and caregivers were recruited through Alzheimer Society provincial chapters and community partners. To ensure inclusivity of underrepresented populations, a targeted community engagement strategy was developed to connect with members of various ethnocultural groups across Canada using a multi‐tiered selection process of cultural community‐based organizations. Qualitative analysis will include thematic analysis using a standard process to code data and generate themes. Quantitative analysis will use descriptive statistics.

Result

This survey is the first of its kind in Canada that investigates the relationships between PLWD and caregivers with their primary health providers and utilizes a defined and consistent approach to community outreach and engagement. The survey bridges the knowledge gap in dementia care research, focusing on inclusivity of ethnocultural communities which has resulted in increased uptake of the survey and will provide richer data for resource creation.

Conclusion

Findings from the survey will inform the ASC‐CFPC collaboration in creating resources to increase physician comfort with managing all patients with dementia. It will also guide the development of new resources and educational materials for PLWD and caregivers. The community engagement strategy will help create and strengthen community relationships with ethnoculturally diverse communities through a mutual knowledge sharing and community building.
The impact of COVID‐19 outbreak on individuals with Alzheimer’s disease: Information released through online news
Authors: Park Eunsun , Kollia Betty , Basch Corey
Published: February 2022

Background

Total confirmed cases for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) have been increased quickly worldwide after the emergence of COVID‐19 in Wuhan, China, in December 2019. As of January 21, 2021, the total confirmed coronavirus cases are 97,736,758 worldwide with 25,124,602 in the United States (Worldometer). Prior to the COVID‐19 pandemic, the incidence of neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson’s disease (PD) had been growing rapidly rendering them major threats to human health. COVID‐19 impacted health care for persons with neurodegenerative diseases. This study reviews current research findings and their online news coverage related to the impact of COVID‐19 outbreak on persons with Alzheimer’s Disease (PWAD) in the 10 months from April 2020 to January 2021 and available resources for caregivers and PWAD.

Method

We searched “COVID‐19 Alzheimer’s Disease” in Google News and obtained the URLs of all online news reports from April 1st 2020 to January 15, 2021 for data analysis. The news stories were: a. in English language, b. non‐duplicate, and c. applicable to Alzheimer’s disease occurrence or symptoms related to COVID‐19 positive cases. The content of the selected new stories is being analyzed for references to: 1. Upload date of news report; 2. Country in which the patients in the report are located; 3. Hospital or University names/studies; 4. Journal or source of the information that is being reported; 5. Alzheimer’s disease signs / symptoms; 6. Physical/ medical comorbidities; 7. Comorbidities / associated neuropsychiatric problems mentioned; 8. Alzheimer’s disease management issues; 9. Age of patients.

Result

The study is in progress. We are currently collecting news stories and are analyzing the data.

Conclusion

This study will provide information how the COVID‐19 pandemic influences the course of AD and emerging self‐management strategies for PWAD.
Memory advocate peers: Piloting a sustainable, replicable, volunteer peer mentor program to support individuals newly diagnosed with dementia and their care partners
Authors: Walter Sarah , Cisek Edward , Taylor James , Taylor Geri , Tornatore‐Mikesh Eleonora C , Levine Jed
Published: February 2022

Background

Alzheimer’s disease and related dementias (ADRD) have an enormous impact on persons living with dementia and their care partners. Care partners of people with dementia are more likely to have depression, anxiety, and be isolated, heightened by events like the COVID‐19 pandemic. Connecting individuals to research has been challenging, especially in diverse populations who are disproportionately impacted by ADRD and health and socioeconomic inequities. The Memory Advocate Peers (MAP) Program aims to address these challenges by building and piloting a sustainable, replicable, volunteer peer mentor program to support individuals newly diagnosed with dementia and their care partners, and help to connect them to services.

Method

The MAP program has been developed and is led by people living with dementia, care partners, community‐based experts in dementia care, and healthcare leaders. The program will give people with dementia and care partners the opportunity to share experiences with a volunteer advocate who has lived experience with dementia, obtain valuable education about how to live well with dementia, connect to community services, and access clinical trials or other research opportunities. Partnerships have been established with New York University‐affiliated neurologists to identify and refer newly diagnosed patients to the program, and with the leading local research programs.

Result

MAP will recruit and train up to 25 advocates to provide twelve months of post‐diagnostic support to 50 clients and care partners (where applicable), with a focus on under‐represented communities. A research study is embedded within the program to evaluate feasibility, as well as participant quality of life, health resource use, impact on psychological wellbeing, and value of research participation.

Conclusion

This pilot will be critical in understanding the impact peer‐to‐peer mentorship can have for both the individual with ADRD and the care partner. It will also be critical to develop best practices to recruit, train and support volunteers serving as these peer advocates. Results from the pilot will be used to improve the program prior to expansion to other regions.
Polypharmacy is associated with functional decline in Alzheimer’s disease and Lewy body dementia
Authors: Borda Miguel German , Tovar Diego , Sonnesyn Hogne , Osterhus Ragnhild , Aarsland Dag
Published: February 2022

Background

We aim to study the effects of the number of medications consumed over a five‐year period after diagnosis on functional decline trajectories in older adults living with AD (Alzheimer’s disease) and LBD (Lewy body dementia).

Methods

This is a longitudinal analysis of a Norwegian cohort study entitled “The Dementia Study of Western Norway” (DemVest). We included 196 patients newly diagnosed with AD (n=111) and LBD (n=85), followed annually for 5 years. A linear mixed‐effects model was conducted to analyze the effect of numer of medications on functional decline measured by the Rapid Disability Rating Scale – 2(RDRS).

Results

The mean of medications consumed at baseline was 4.18 ∓ 2.60, for AD 3.92 ∓ 2.51 and LBD 4.52 ∓ 2.70. The number of medications used increased during the follow‐up; at year five the mean for AD was 7.28 ∓ 4.42 and for LBD 8.11 ∓ 5.16. Comorbidity and Neurophysichiatric symtoms scores were significantly higher in the LBD group compared to AD, meanwhile no differences in MMSE. The use of more medications was associated with faster functional decline in AD ( Est 0.04, SE 0.01, p‐value 0.003 ) and LBD ( Est 0.08, SE 0.03, p‐value 0.008 ) after adjusting by age, sex, comorbidity, Neurophysichiatric symtoms and cognition. For each medication added during the follow‐up function decreased by 1% for AD and 2% for LBD.

Conclusions

The more medications used, the greater is the functional decline in AD and LBD. Medications in older adults with dementia should be used cautiously
Associations between amygdala volume and trajectories of neuropsychiatric symptoms in Alzheimer’s disease and dementia with Lewy Bodies
Authors: Jaramillo‐Jimenez Alberto , Giil Lasse Melvær , Tovar Diego , Borda Miguel German , Ferreira Daniel , Brønnick Kolbjørn , Oppedal Ketil , Aarsland Dag
Published: February 2022

Background

The potential role of the amygdala for neuropsychiatric symptoms (NPS) in dementia is not well known, especially in dementia with Lewy bodies (DLB). Cross‐sectional studies have proposed the associations between amygdala volume and NPS in Alzheimer’s Disease (AD). However, less is known about the association between amygdala volume and longitudinal trajectories of NPS. We aimed to analyze the association between amygdala volume and the longitudinal trajectories of NPS in AD and DLB.

Method

89 patients with mild dementia were included (AD = 55; DLB =34) in this secondary analysis of a longitudinal cohort study. Baseline amygdala volume was segmented from structural magnetic resonance images (sMRI) using a semi‐automatic method (Freesurfer 6.0). NPS were assessed annually over five years with the Neuropsychiatric Inventory (NPI) frequency × severity item‐scores. NPI item‐scores ≥ 4 were considered clinically relevant symptoms. Mixed‐effects logistic regression models were conducted in the whole sample and then in AD and DLB separately. Amygdala volume was included as a predictor of each NPS (i.e. NPI item‐score ≥ 4) over time. The models were adjusted for key demographic variables and diagnostic, as well as for center of sMRI acquisition and cognition.

Result

The cohort characteristics are shown in Table 1. Intracranial volume‐normalized amygdala volumes were comparable between AD and DLB patients. After correcting adjusted models for multiple testing, a lower odds of apathy scores ≥ 4 over time was found in patients with larger amygdala volume at baseline (OR:0.36; 95% CI: 0.21 – 0.64; p < 0.001; FDR = 0.002), with no significant effects of diagnostic (OR: 1.11; 95%CI: 0.56 – 2.17; p = 0.769; FDR = 0.846), Figure 1. The subgroup analyses showed significant results for apathy in both DLB and AD: (DLB (OR: 0.37; 95% CI: 0.16 – 0.87; p = 0.023) and AD (OR: 0.35; 95% CI: 0.15 – 0.79; p = 0.012).

Conclusion

Smaller amygdala volumes in people with mild dementia were associated with a higher risk of clinically relevant apathy, in both AD and DLB patients, during the 5 years study period. This association between apathy and amygdala might reflect damage in circuits underlying behavioral and cognitive avoidance.
A proposition for analyses and reporting standards for structural and functional magnetic resonance imaging of the noradrenergic locus coeruleus
Authors: Yi Yeo‐Jin , Lüsebrink Falk , Maass Anne , Betts Matthew , Ziegler Gabriel , Yakupov Renat , Kreißl Michael , Speck Oliver , Düzel Emrah , Hammerer Dorothea
Published: February 2022

Background

The noradrenergic locus coeruleus (LC) in the brainstem shows earliest signs of protein pathologies in neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Its small size (about 3‐4mm in width and 15 mm in length) makes it less suitable for Positron Emission Tomography (PET) investigations, so the past decade has seen a steep rise in structural and functional Magnetic Resonance (MR) studies aiming to characterise the LC's changes in ageing and neurodegeneration. However, given its position in the brainstem and small volume, great care has to be taken to yield methodologically reliable MR results as imprecisions in spatial transformations of functional data in the range of 2‐3mm might make LC activations at the group level effectively disappear (Figure 1B). Here, we suggest a post‐processing pipeline and set of quality control protocols which will allow LC researchers to reach the spatial precision necessary for investigating this small but potentially impactful brain structure.

Method

Using a combination of available toolboxes (SPM, ANTs, FSL, FreeSurfer), individual 3T scans for structural and functional LC characterisation are transformed into MNI space via a study‐specific template (Figure 1A). Concatenation of independently optimised transformation steps minimises interpolation applied to the data. Following this, spatial misalignment in individual MNI‐transformed are assessed using Euclidean distance (ED) measures using slice‐specific centres of structural LC masks and distance to landmarks defined based on salient anatomical features of mean functional LC images, respectively.

Result

Median Euclidean Distance of all landmarks on the transformed functional as well as structural LC imaging data were below 2 mm, thereby falling below the typical LC width of 2.5 mm shown in post‐mortem data (Fernandes et al., 2012), or half of the maximum width of the standard‐space LC mask of 4 mm (Keren et al. 2009).

Conclusion

With the set of spatial post‐processing steps outlined in the poster and available for download soon, we hope to have taken a first step towards establishing reporting standards of LC imaging data and to give readers interested in LC imaging a starting point for more reliable analyses of structural and functional MR data of the LC.
Neuroimaging‐derived phenotypes in the European Prevention of Alzheimer Dementia (EPAD) Cohort Study
Authors: Lorenzini Luigi , Ingala Silvia , Wink Alle Meije , Kuijer Joost , Wottschel Viktor , Sudre Carole H. , Haller Sven , Molinuevo Jose , Gispert Juan Domingo , Cash David M. , Thomas David L. , Vos Sjoerd , Carrasco Ferran Prados , Petr Jan , Wolz Robin , Palombit Alessandro , Schwarz Adam J. , Chetelat Gaël , Payoux Pierre , Di Perri Carol , Pernet Cyril , Frisoni Giovanni B. , Fox Nick C. , Ritchie Craig W. , Wardlaw Joanna M. , Waldman Adam , Barkhof Frederik , Mutsaerts Henk‐Jan
Published: February 2022

Background

Neuroimaging biomarkers in large‐scale multimodal studies have proven effective for early diagnosis. Image‐derived phenotypes (IDPs) are summary features derived from modalities such as magnetic resonance imaging (MRI). We provide an overview of the IDPs computed from the European Prevention of Alzheimer Dementia (EPAD) cohort study, a multi‐center European study including multimodal brain MRI.

Method

Baseline data from the first 1500 participants of the EPAD LCS were included. The imaging protocol consists of core (3D‐T1w, 3D‐FLAIR, 2D‐T2w, 2D‐T2*), and advanced (resting‐state fMRI, SWI, diffusion MRI, and ASL) sequences. 3D‐T1w IDPs consisted of regional volumes derived from FreeSurfer v6.0 and the Learn Embeddings for Atlas Propagation (LEAP) segmentation pipelines and 3D‐FLAIR IDPs were white matter hyperintensity (WMH) volumes measured by Bayesian Model Selection (BaMoS). Mean functional connectivity of rs‐fMRI networks was extracted with FSL MELODIC and dual‐regression analyses. For diffusion‐weighted imaging, we used FSL TBSS to quantify 48 regional fractional anisotropy (FA) values according to the JHU atlas of white matter tracts. ExploreASL was used to calculate mean Cerebral blood flow (CBF) and spatial coefficient‐of‐variation (sCoV) from ASL images. To evaluate the biological relevance of IDPs, we assessed their relationship with non‐imaging phenotypes.

Result

A total of 358 core and 119 advanced IDPs were derived. GM volume was inversely correlated with age, with stronger effects in medio‐temporal areas (Figure 1). Regional WMH volumetrics showed mostly frontal and parietal WM lesions that were associated with aging (Figure 2). Heterogeneous changes in within‐network functional connectivity were observed with older age, with mild differences between CDR 0 and 0.5 contrasts, mostly related to the default‐mode and frontoparietal networks (Figure 3). Age was also associated inversely with skeletonised FA values. Stronger reductions appeared in amyloid positive participants (Figure 4).

Conclusion

We show the relevance of IDPs from the EPAD neuroimaging dataset. The observed relationships with non‐imaging phenotypes confirm their biological relevance and are in agreement with previous studies. The proposed IDP framework may constitute a valuable resource for researchers using EPAD data, promoting reproducibility of results and easily adaptable for other studies and cohorts.
Abnormal neural oscillations depicting excitatory‐inhibitory imbalance are distinctly associated with amyloid and tau depositions in Alzheimer's disease
Authors: Ranasinghe Kamalini G. , Verma Parul , Cai Chang , Xie Xihe , Kudo Kiwamu , Gao Xiao , Lerner Hannah M. , Mizuiri Danielle , Strom Amelia , Iaccarino Leonardo , La Joie Renaud , Miller Bruce L. , Tempini Maria Luisa Gorno , Rankin Katherine P. , Jagust William J. , Vossel Keith A. , Rabinovici Gil D. , Raj Ashish , Nagarajan Srikantan S.
Published: February 2022

Background

Excitation‐to‐inhibition (E/I) imbalance is believed to be a key contributor of synaptic and network degeneration in Alzheimer’s disease (AD)(Frere and Slutsky, 2018). Extensive preclinical research on transgenic animal models of AD have demonstrated neuronal and circuit level E/I imbalance mediated by amyloid‐beta (Aβ) and abnormally phosphorylated tau proteins (Harris et al., 2020; Palop and Mucke, 2016). However, the mechanisms of E/I imbalance leading to disrupted networks and their relationships to Aβ and tau in humans remain poorly understood.

Method

In this multimodal imaging study in patients with AD (n=20 AD patients; n=35 age‐matched controls; Table‐1), we first examined the spectral changes in oscillatory brain rhythms using magnetoencephalography and their relationships to tau and amyloid‐beta (Aβ) accumulation in PET imaging (flortaucipir and 11C‐PiB, for tau and Aβ, respectively). Next, we estimated parameters of a linear neural mass model (Raj et al., 2020) that best fit the observed spectra, and examined the relationships between model parameters for excitatory and inhibitory neural sub‐populations, and tau and Aβ accumulations.

Result

We found that neuronal hypoactivity was associated with tau while hyperactivity was associated with Aβ (Figure 1). We also demonstrated E/I imbalance in patients with AD, depicted as abnormal excitatory and inhibitory neuronal parameters in a linear neural mass model that reproduced the empirical macroscopic power spectra (Figure 2). The abnormal excitatory and inhibitory neuronal parameters showed distinct associations with tau and Aβ—higher tau correlated with a longer excitatory time‐constant, whereas higher Aβ correlated with a longer inhibitory time‐constant (Figure 3).

Conclusion

The unique contribution of the collective finding in the current study is to demonstrate how abnormalities in the oscillatory power spectrum in AD is mechanistically linked to impaired function of excitatory and inhibitory neuronal populations that are in turn associated with tau and Aβ accumulations. Neural oscillations are modulators of rate and timing of neuronal spiking and have a key role in governing the neuronal excitability (Siegel et al., 2012). The multimodal neuroimaging in AD patients in the current study demonstrate how different frequency oscillations are distinctly affected by Aβ and tau, and offer new perspectives for network stabilizing therapies.
Advanced diffusion‐MRI models reveals sex‐specific differences in white matter organization in patients with mild cognitive impairment
Authors: Mishra Virendra R. , Ritter Aaron , Caldwell Jessica Z.K.
Published: February 2022

Background

Recent literature suggests that free‐water corrected (fiso) diffusion MRI (dMRI) measures provide higher sensitivity as compared to conventional single‐tensor (ST) dMRI measures to understand white‐matter (WM) changes due to neurodegeneration. However, fiso‐corrected dMRI measures are still biased at crossing‐fiber regions (CFR) of WM which are shown to be around 90% of the total WM voxels with conventional dMRI data acquisition. In this study, we systematically compared dMRI measures from ST‐dMRI, fiso‐corrected ST‐dMRI measures, and measures from advanced dMRI models such as Diffusion Kurtosis Imaging (DKI) and Neurite Orientation Distribution and Density Imaging (NODDI) which are sensitive to CFRs. We hypothesize that these advanced dMRI models will be sensitive in understanding sex‐specific WM organizational changes at regional level in patients with Alzheimer’s disease (AD)‐related mild cognitive impairment (MCI).

Method

40 healthy controls [HC; 21 Females (F), 19 Males (M)] and 38 MCI participants [13F, 25 M] were recruited at our center. MCI diagnoses were based on expert consensus between a neurologist (AR) and a neuropsychologist (JC) using results of a neuropsychological test battery and the Clinical Dementia Rating (CDR) interview. Isotropic 1.5mm3 multi‐shell dMRI (b‐values=500s/mm2, 1000s/mm2, and 2500s/mm2) each with identical 71 diffusion‐encoding directions was acquired on a 3T Siemens Skyra scanner for every participant using the CMRR sequence. 8 uniformly interspersed non‐diffusion‐weighted (b0) images were also acquired in the same run. ST, fiso‐corrected, DKI, and NODDI dMRI measures were estimated for every brain voxel in‐house using the standard analytic tools. WM was skeletonized using FSL tools and statistical comparisons were done non‐parametrically using PALM tools. GLM was utilized to test for sex‐specific group effect. Significance was established at family‐wise error correction (FWE) pcorr<0.05.

Result

Thalamocortical tracts of males in both HC and MCI showed a significantly higher axonal kurtosis (AK) and orientation density (ODI) derived from DKI and NODDI when compared to within‐group females. DKI also revealed presence of higher axonal water fraction (AWF) along the entire WM‐tracts between HC‐female and HC‐male, and lower mean kurtosis (MK) along the thalamic‐cortical tracts in HC‐females as compared to MCI‐females.

Conclusion

Advanced dMRI‐models are sensitive to understand sex‐specific WM disorganization due to healthy ageing and MCI.