bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain Healthy Soul Food Diet Intervention Among Older African Americans
Authors: Shaw Ashley R.
Published: December 2023

Background

Alzheimer’s disease (AD) poses a major public health crisis, especially among African Americans who are disproportionally burdened by AD. Emerging evidence suggests that up to half of AD cases are a result of modifiable cardiovascular (CV) or metabolic risk factors related to poor diet such as elevated blood pressure, arterial stiffness, obesity, and diabetes, all of which disproportionately affect African Americans. Given the high prevalence of CV related risk factors in the African American community, prevention strategies are critical for reducing the disproportionate impact of AD among African Americans.

Method

We conducted a single arm 12‐week pilot in 2 waves (n = 20 African Americans) to assess feasibility and acceptability of an adapted brain‐healthy soul food diet intervention (MIND+SOUL) as measured by recruitment rates, retention rates, adherence, and satisfaction. The intervention encompassed skill building cooking classes, health coaching, and weekly groceries. We also evaluated preliminary efficacy of the MIND+SOUL diet intervention on CV risk and nutritional health status as measured by body composition, blood pressure, cholesterol, NHANES diet screening questionnaire, and beta carotene spectrophotometer. Lastly, we assessed change in cognition as assessed by the NIH Toolbox (NIH‐TB domains: memory, language, reading, vocabulary, processing speed, and executive function).

Result

A total of 20 African Americans participated in the study with a retention rate of 90%. Most participants perceived the MIND+SOUL diet as feasible to follow (88.9%) and perceived the MIND+SOUL diet as effective in improving their overall health (77.8%). The median acceptability score was 67 out of 100 in which participants suggested modifications to the health coaching design and dissemination. Additionally, participated completed baseline and 12‐week CV, nutritional health status, and cognitive assessments.

Conclusion

Findings from this study indicate that older African Americans have a high interest in culturally tailored diets. Additionally, findings from this study will inform the development of a full‐scale randomized control trial that will test the efficacy of the MIND+SOUL intervention among older African Americans across a larger geographical area.
Alzheimer’s disease risk genes modulate interferon‐responsive microglia
Authors: McQuade Amanda , Castillo Vincent Cele , Drager Nina , Kampmann Martin
Published: December 2023

Background

Human genetic studies and quantitative trait loci (eQTL) analyses have implicated microglia, the innate immune cells of the brain, as critical players in Alzheimer’s disease (AD). In response, the field has focused on defining microglial transcriptional states across many models of neurodegeneration. Integrating these studies, we find several microglial activation states commonly enriched in AD. These include Disease Associated Microglia, Antigen‐Presenting Microglia, and Interferon‐Responsive Microglia. To truly make use of this data, we now must move towards understanding the functional consequence of these microglial activation states and uncovering the mechanisms that drive changes in cell states during disease.

Method

To determine regulators of the interferon‐responsive microglial activation state, we performed a functional genomic screen using CRISPR interference (CRISPRi). To avoid bottlenecking of CRISPR guide RNAs and accommodate the large numbers of cells needed for screening, we implemented a novel transcription‐factor driven approach to differentiate iPSC‐derived microglia. After differentiation, microglia harboring individual gene knockdowns were primed with type I interferon and screened on expression of IFIT1, a key marker of the interferon‐responsive microglial state.

Result

These experiments have uncovered both canonical regulators of interferon signaling as well as novel regulators of the interferon‐responsive microglial state. Furthermore, several known AD risk genes were shown to inhibit microglial entry into this state, suggesting a potential mechanism whereby these nodes may influence disease risk.

Conclusion

Recent transcriptomic studies have uncovered significant heterogeneity of microglial states including the discovery of several disease associated states. However, it remains unclear whether these states represent beneficial, disease‐fighting functions or detrimental, disease‐promoting functions. Gaining the ability to selectively control entry into specific microglial states will allow novel investigations into how these specific microglial states interact with and guide disease trajectories.
Sex/Gender Differences in the Diagnosis of Pain by Cognitive Status
Authors: Milani Sadaf Arefi , Fang Kuo Yong‐ , Downer Brian , Berenson Abbey , Doulatram Gulshan , Raji Mukaila
Published: December 2023

Background

Underdiagnosis of pain is common in women and in those with Alzheimer’s disease and related dementias (ADRD). However, sex/gender differences in pain interference, defined as pain that interferes with daily activities, have not been examined along the cognitive spectrum. We assess sex/gender differences in odds of physician‐diagnosed and self‐reported pain, by cognitive status: normal, cognitively impaired but not dementia (CIND), and dementia.

Methods

We will use data from the 2006 to 2018 waves of the Health and Retirement Study (HRS) linked to Medicare Claims. We will include participants aged 66 and older with at least one year of continued enrollment in Medicare. Our pain diagnosis measure will incorporate self‐reported pain interference, herein referred to as pain, with pain diagnosis in a three‐level variable: no pain, undiagnosed pain (self‐reported only), and diagnosed pain. Cognitive status (normal cognition, CIND, dementia) was measured using the Telephone Interview for Cognitive Status. We will use generalized estimating equation models to calculate gender disparities in the odds of pain diagnosis, by cognitive status. Here we present preliminary results, using cross‐sectional data from the 2018 HRS (n = 7,588) to examine self‐reported pain by cognitive status. We include descriptive statistics and logistic regression models, adjusted for age, race/ethnicity, years of education, marital status, depression, diabetes, arthritis, and obesity.

Results

Women more often reported pain compared to men for those with normal cognition (women: 27.7%, men: 18.7%; p<0.001) and CIND (women: 32.6%, men: 18.9%; p<0.001). Among those with dementia, 29.9% of women and 22.7% of men reported pain (p = 0.108). For those with normal cognition and CIND, women had higher odds of reporting pain compared to men [normal cognition odds ratio (OR): 1.34, 95% confidence interval (CI): 1.16, 1.55); CIND OR: 1.84 95% CI: 1.38. 2.47]. However, no sex/gender disparity is observed among those with dementia (95% CI: 1.13, 95% CI: 0.66, 1.94).

Conclusions

In our preliminary analysis we found that the sex/gender disparity in self‐reported pain interference is not present among those with dementia. The final version of this work will incorporate the Medicare data from 2006 to 2018 so that we can assess sex/gender differences in clinician‐documented pain diagnosis.
Meta‐analysis of NIH Alzheimer’s Disease‐Related Dementias (ADRD) programs responsive to the National Plan to Address Alzheimer’s Disease (AD)
Authors: McCartney Amber J , Shukla Arvind , Yin Xiling , Dodson Sara , Bryant Erin , Corriveau Roderick A
Published: December 2023

Background

AD/ADRD diseases currently impact more than 6 million people in the US. Rare forms of AD/ADRD are caused directly and unambiguously by genetic mutations. However, most AD/ADRD burden is complex in etiology and thought to result from an interplay among multiple incompletely understood genetic, biochemical, lifestyle, environmental and psychosocial risk factors. Moreover, risk factors interact with other health factors to impact AD/ADRD outcomes. For example, while the most common dementia diagnosis is AD, research over the past decade revealed most people with a diagnosis of AD have multiple brain pathologies, other comorbidities, and many people diagnosed with clinical AD do not have AD pathology at all. This new knowledge highlights the importance of better understanding dementia syndromes, and the relationships among them, to increase chances of developing effective interventions. The NINDS partners with the NIA, the NIH lead for AD/ADRD, in the NIH response to the National Plan. NINDS leads ADRD including frontotemporal dementia (FTD), Lewy body dementias (LBD), vascular contributions to cognitive impairment and dementia (VCID) and multiple etiology dementias (MED). This project aims to evaluate NIH and the ADRD field’s responsiveness to ADRD research milestones from triennial NINDS ADRD Summits by mapping NIH‐funded research activities to ADRD milestones.

Method

The approach used text‐based analysis/mining of grant titles, abstracts, and specific aims to map awards and activities to ADRD milestones. Mappings were vetted by expert concurrence. The ongoing study includes new or competitively renewed NIH ADRD awards starting from fiscal year 2017. Findings help NIH to better understand the state of the field, identify research gaps and opportunities for future efforts, and enable public communication of research activities with an accurate, accessible, compact, and updatable data visualizations.

Result

Results indicate the approach is feasible, and importantly the field and NIH have largely been responsive to the ADRD milestones in the National Plan to Address AD.

Conclusion

The analysis points to several cross‐cutting ADRD research areas that may benefit from increased attention going forward, including health equity, the multiple etiology hypothesis of common dementias, emerging risk factors for common dementias (e.g. COVID‐19, TBI, and TDP‐43 proteinopathy), and clinical trials.
Look AHEAD Sleep: Study Design and Baseline Characteristics
Authors: Hayden Kathleen M. , Neiberg Rebecca H. , Bertisch Suzanne , Chen Haiying , Culkin Margaret C. , Dennis Stephen , Ding Jingzhong , Garcia Katelyn R , Rapp Stephen R. , Redline Susan , Blanco Jeannette Rosales , Sachs Bonnie C. , Sanderlin Ashley H. , St‐Onge Marie‐Pierre , Espeland Mark A. , Wagenknecht Lynne E , Spira Adam P.
Published: December 2023

Background

Older adults with obesity (body mass index [BMI] ≥30 kg/m2) and type‐2 diabetes (T2D) have increased risks for mild cognitive impairment (MCI) and dementia. Sleep‐disordered breathing (SDB) is common in older adults and those with T2D and obesity, and has been linked to increased risk of Alzheimer’s disease (AD) and Alzheimer’s disease‐related dementias (ADRD). SDB may represent a unique and modifiable pathway that elevates the risk of cognitive decline among patients with T2D and obesity. Yet, few studies have examined associations between SDB and cognitive outcomes among persons with T2D and obesity. Addressing this gap is critical as the prevalence of metabolic disorders is increasing, placing a growing population at risk for MCI, and AD/ADRD. Look AHEAD Sleep (LA‐Sleep) was designed to study associations of SDB and circadian rhythms with cognitive function in older adults with a history of these conditions. Here, we report initial baseline characteristics of LA‐Sleep cohort.

Method

Participants enrolled in Look AHEAD Aging (LA‐A), a continuation of the Look AHEAD cohort study, were eligible to participate in LA‐Sleep. Participants completed cognitive assessments and were randomized to have a sleep assessment in either Year 1 (2022‐2023) or 2 (2023‐2024). Year 1 participants completed sleep questionnaires and received in‐home sleep assessment devices (WatchPAT and ActiGraph) and a sleep diary by mail.

Result

Of 1,522 who consented to LA‐A, 952 agreed to LA‐Sleep and to date, 161 have provided year 1 WatchPAT (n = 161) or Actigraph (n = 107) data. There were more females (55.3%) than males; the average (±SD) age was 76.1±5.4 y; average BMI was 34.3±7.0; and 10.6% of the sample was Non‐Hispanic Black, 6.2% Hispanic, and 76.4% Non‐Hispanic White. Most had more than a high school education (90.1%). Of those with obesity in 2018‐2020, 20.0% had severe SDB (apnea hypopnea index ≥30). Overall mean actigraphic‐estimated sleep duration was 7.1±1.4 hours, sleep efficiency (total sleep time/time in bed) was 87.0%, and wake‐after‐sleep‐onset was 62.5±31.0 minutes/night.

Conclusion

Among an older adult cohort with T2D and overweight or obesity, a high proportion of participants have severe SDB and high levels of sleep fragmentation, placing them at increased risk for cognitive impairment.
A Living Lab in the Quebec’s Homes for older adults with a neurocognitive disorder: aiming to improve the personalization of long‐term care and the self‐determination of residents and their relatives
Authors: Hudon Carol , Ribon‐Demars Alexandra , Batcho Charles , Gaied Nouha Ben , Blanchette Andreanne , Bolduc Francois , Charest Caroline , Cote Nancy , Collomb‐d'Eyrames Olivier , Duchesne Simon , Feillou Isabelle , Fortin Elise , Gagnon Caroline , Giguère Andrée , Giguère Anik , Guénette Line , Hardy Marie‐Soleil , Laberge Maude , Labonte Marie‐Eve , Langevin Louise , Lapierre Judith , Macoir Joel , McFadyen Bradford James , Methot Pierre‐Olivier , Monetta Laura , Morisset Anne‐Sophie , Peters Valerie , Raymond Emilie , Routier Francois , Singamalum Sonia , Tanguay Pascal , Voyer Phillippe
Published: December 2023

Background

The “ Quebec’s Homes for Older Adults with a Neurocognitive Disorder ” (QHOA) model aims to improve the quality of residential and long‐term care environments for people losing their autonomy. Considering the major paradigm shift behind the QHOA philosophy, it seemed timely to co‐construct a Living Lab‐type structural organisation whose main mission will be to contribute to the sustainability of the new model.

Objectives

Since 2021, we have been co‐constructing links between scientists, decision‐makers, staff (carers, cooks, housekeepers, etc.), QHOA stakeholders and, above all, the community and its seniors. Our structure is a Living Lab and the main objective is to cyclically and participatively co‐construct a set of solutions applicable to QHOAs. Our work will encourage the design and development of sustainable solutions by considering human (e.g., self‐determination, personalization of care), environmental (e.g., layout and design, camouflage strategies), technological (e.g., sensors, cameras, connected watches and scales, artificial intelligence, software for care and medication), work organization, and continuous training of stakeholders.

Results

The co‐construction process involved more than 40 researchers, clinicians, decision‐makers, or stakeholders. We have all been able to delineate the structure of the Living Lab and how knowledge will be disseminated, rallied, and promoted. This presentation will resume the main steps (including successes and challenges) of our work.

Implications

A Living Lab is a place for collaboration, exchange, and co‐creation. The actors in the field have the most relevant knowledge of the living context in which the projects will be deployed. Our intersectoral team (20 fields of expertise) will provide the scientific knowledge to ensure the sustainability and ongoing development of the QHOA model.
Gender differences in the mediational pathway between trauma, depression and subjective cognitive decline
Authors: Brown Monique J , Esiaka Darlingtina , Viswanathan Jaya
Published: December 2023

Background

Adverse childhood experiences (ACEs) have been linked to subjective cognitive decline (SCD) in later life, which may be a precursor for Alzheimer’s disease. However, studies examining the potential mechanisms between ACEs and SCD as well as the differential role that gender might play in these pathways are lacking. The aim of this study was to assess how gender influences the association between ACEs, depression and SCD.

Method

Data were obtained from 14,630 respondents (6,254 men and 8,376 women) from the 2021 US Behavioral Risk Factor Surveillance System survey. Trauma was operationalized as the experience of ACEs. A depression categorization was based on respondents’ self‐report of ever being informed of having a depressive disorder. SCD was operationalized as respondents reporting having experienced increasing confusion or memory loss in the past 12 months. Crude and adjusted stratified path analyses using PROC CALIS were conducted to determine the direct and indirect associations between ACEs, depression, and SCD overall and by gender.

Result

Preliminary analyses show that in the overall study population, respondents who reported experiencing ACEs were more likely to report depression (B = 0.165; p<0.0001) and those who reported a depression diagnosis were more likely to report SCD (B = 0.191; p<0.0001) in the past year. There was also a direct positive association between ACEs and SCD (B = 0.085, p<0.0001) where respondents with a history of ACEs were more likely to report SCD. Depression mediated the association between ACEs and SCD (B = 0.032; p<0.0001) Stratified path analyses showed similar findings for men and women where depression was a mediator in the relationship between ACEs and SCD (men: B = 0.025; p<0.0001; and women: B = 0.036; p<0.0001).

Conclusion

Depression mediated the association between ACEs and SCD in the overall population, and among men and women. There was no moderating role of gender in the mediational pathway between ACEs, depression and SCD. Further analyses will be conducted to elucidate the interaction effects in these data. Future studies should assess the moderating role of gender in alternative mediational pathways such as examining substance use, and PTSD as potential mediators in the relationship between ACEs and SCD.
Clinical stage Alzheimer’s therapy, NNI‐362 promotes TH+ neurons associated with a reversal of motor deficits in AAV‐alpha synuclein model, leaving alpha synuclein unchanged
Authors: Kelleher‐Andersson Judith , Noe Emelie , Robin Laurie , Bezard Erwan , Turner R. Scott
Published: December 2023

Background

NNI‐362 is a novel small molecule identified by phenotypic screening to discover compounds that promote new neurons from human neural progenitor cells and have neuroprotective capacity. A placebo‐controlled, double‐blind Phase 1a trial examined the safety and tolerability of NNI‐362, as well as a pharmacodynamic outcome ‐ the level of plasma p‐tau181, a blood‐based biomarker specific to Alzheimer’s disease (AD) pathology. Results in animal models of other age‐related disorders suggest NNI‐362 has the potential to halt or reverse AD and PD clinically.

Method

An AAV‐alpha synuclein rat model of Parkinson’s disease (PD) (MOTAC, France) was used to examine the effects of NNI‐362 treatment. This model results in anosmia and motor phenotypes, loss of TH+ neurons, and diminished adult‐born neurons triggered by alpha‐synuclein expression in the SNpc. NNI‐362 and placebo were formulated as a lipid suspension and administered orally once daily for up to 6 weeks post‐stabilization of AAV‐synuclein expression. At 8 weeks, brains were removed, and the SNpc sectioned and stained for TH+ neurons, alpha‐synuclein, and BrdU+ adult‐born neurons. Results were compared to AAV‐GFP‐injected, vehicle‐treated rats ‐ in groups of M or F and treatment or placebo (n = 14/group, 7F/7M).

Result

Brain permeable therapy NNI‐362 did not alter alpha‐synuclein levels, but promoted BrdU+ neurons in the substantia nigra. Thus, generating and protecting TH+ neurons was associated with reversing motor deficits in females. No motor deficits and no BrdU+ neuron deficits were observed in AAV alpha‐synuclein treated males (twice run model), as such no amelioration by NNI‐362 treatment.

Conclusion

Oral NNI‐362 may be a cause‐agnostic therapeutic ‐ promoting region‐specific new neurons, TH+ neuronal protection, and behavioral improvement when induced by dopaminergic deficit, including neurogenesis deficit. After AAV‐alpha‐synuclein induction of 2 weeks, and then followed by chronic NNI‐362 treatment, both behavior and neuron numbers were no different than AAV‐GFP control levels in this clinically‐relevant experimental model of PD.
Heuristic evaluation and usability testing of a functional dementia stages app for Hispanic family caregivers
Authors: Arcia Adriana
Published: December 2023

Background

Hispanic family caregivers of persons with Alzheimer’s disease and other dementias are not getting the anticipatory guidance they need about how functional abilities will change as dementia progresses. Existing informational resources are overwhelming to navigate and written at a high reading level. Furthermore, professional assessment of functional abilities is not universally available. Innovative, tailored approaches are needed. Our aim was to develop and test a mobile application, the Interactive Functional Assessment Staging Navigator (I‐FASTN), to support Hispanic family caregivers’ assessment of care recipients’ functional stage of dementia in either English or Spanish.

Method

We conducted heuristic evaluation with informatics experts (N = 5, English only) and usability testing with caregivers (n = 10 English, n = 10 Spanish). Participants attempted a series of tasks with the app using a think‐aloud protocol and then rate the usability of the app using mobile app heuristics (experts) and two usability instruments (caregivers). Sessions were recorded and transcribed. For heuristic evaluation, we tabulated the number of usability problems by category: cosmetic, minor, major, and catastrophic. For usability testing, recordings, notes, and transcripts were content analyzed to extract usability problems, suggestions for improvement, desired app features, and other feedback.

Result

Refinements to the app were made after each of the five evaluations to address the problems encountered. Caregivers’ mean usability scores were high (4.6 and 4.7 out of 5.0), reflecting good usability overall. Chief usability problems were a confusing tutorial and difficulty finding the app’s side menu. These will be addressed by creating a video tutorial and moving all menu items to the home screen. The app was very well received by caregivers, who indicated that the concise, illustrated content met their informational needs. However, analog alternatives are still needed by caregivers unaccustomed to using apps as they had difficulty moving on from even the simplest screens (see Figure 1a).

Conclusion

Caregivers are not receiving informational support in a way that meets their needs. The focus should be on providing concise information that addresses the practical aspects of caregiving, tailored to the care recipient’s functional stage.
Role of Peroxiredoxin 6 in the Development of Tau Pathology
Authors: Pankiewicz Joanna E. , Lizińczyk Anita M , Franco Leor A. , Diaz Jenny R , Gootman Alexandra , Sadowski Martin J.
Published: December 2023

Background

In Alzheimer’s disease (AD) and fronto‐temporal dementia excess of hyperphosphorylated tau (p‐tau) assembles into neurofibrillary tangles (NFTs). NFT‐bearing neurons are associated with A1 neurotoxic astrocytes and neurodegenerative phenotype microglia (MGnD). A1 astrocytes lose their neuron‐supporting properties and along with MGnD contribute importantly to the degeneration of NFT‐bearing neurons. MGnD and A1 astrocytes also reciprocally stimulate their pathological phenotypes. Factors endowing astrocytes with resistance to A1 transformation remain unknown. Astrocytes express peroxiredoxin 6 (PRDX6) protein, which glutathione peroxidase and phospholipase 2 enzymatic activities enable repair of oxidatively damaged cell membranes and cell‐to‐cell signaling. PRDX6 upregulation has been noted in astrocytes associated with NFT‐bearing neurons in AD, yet its precise role in the development of tau pathology remains unknown. To this end we created new MAPTP301S transgenic mouse lines featuring Prdx6 haplodeficiency and hemizygous knock‐in of the overexpressing Prdx6 transgene.

Method

MAPTP301S (PS19/Prdx6+/+) mice were crossed with Prdx6−/− mice and with Prdx6129X1/SvJ allele knock‐in mice, which feature wild‐type PRDX6 overexpression. Resulting lines PS19/Prdx6+/−, PS19/Prdx6+/+, and PS19/Prdx6Tg showed 0.4:1:2 ratio of brain Prdx6 mRNA level, while hTau and Gfap mRNA levels were similar. All lines were neuropathologically characterized at the age of 9.5 months.

Result

Brain atrophy determined by quantifying hippocampal and lateral ventricular volumes and the hippocampal p‐tau load show inverse relations with the Prdx6 gene dose. The load of GFAP+ astrocytes and the C3+/GFAP+ ratio used as a surrogate A1 phenotype marker also vary inversely with the Prdx6 expression. The load of IBA1+ microglia show inverse relation with the Prdx6 gene dose, while the CD68+/IBA1+ index used as a surrogate marker of microglia phagocytic activity show direct correlation.

Conclusion

Attenuation of the pathological phenotype in PS19/Prdx6Tg line and its worsening in PS19/Prdx6+/− line evidence a neuroprotective role of PRDX6 in tau‐mediated neurodegeneration. Observed inverse relation between the Prdx6 gene dose and astrocytic C3 expression and microglia activation suggests PRDX6 endows astrocytes with resistance to A1 transition, which in turn hampers microglia activation. Analysis of astrocyte and microglia transcript from PS19/Prdx6+/−, PS19/Prdx6+/+, and PS19/Prdx6Tg lines focused on A1 and MGnD activation markers is underway.
Sleep apnea‐related hypoxemia, not sleep fragmentation, is associated with white matter hyperintensities in older adults
Authors: Berisha Destiny E , Rizvi Batool , Chappel‐Farley Miranda G. , Taylor Lisa M. , Sattari Negin , Dave Abhishek , Chen Ivy Y. , Neikrug Ariel , Benca Ruth M , Yassa Michael A. , Mander Bryce A
Published: December 2023

Background

Sleep apnea is a type of sleep‐disordered breathing that increases risk for Alzheimer’s disease‐related pathology potentially through cerebrovascular pathology, likely exacerbated by two features of sleep apnea: intermittent hypoxia and sleep fragmentation. White matter hyperintensities (WMH), a marker of small vessel cerebrovascular disease, increase in aging and in AD. Here, we tested the hypothesis that apnea‐related hypoxemia severity, and not sleep fragmentation, are associated with WMH volume in older adults.

Methods

Thirty‐two older adults (73.4±5.3 years, 19 female, AHI = 15.2±18.9) were evaluated with overnight polysomnography (PSG). Apnea severity was quantified using the Apnea‐Hypopnea Index (AHI), Respiratory Disturbance Index (RDI), and blood oxygen desaturation (Oxygen Desaturation Index (ODI), duration, frequency of ≥4% desaturations, and desaturation nadir) stratified by sleep stages. T1‐MPRAGE and T2‐FLAIR scans were acquired using a 3T Siemens scanner. Total WMH volumes were derived using a semi‐automated algorithm. Overnight memory retention was assessed using the change in the lure discrimination index (LDI) for the emotional version of the Mnemonic Discrimination Task.

Results

Traditional measures of apnea severity and sleep fragmentation were not significantly associated with global WMH volume. However, both max duration of oxygen desaturation events (r = 0.44, p = 0.011) and max oxygen desaturation percentage (in rapid‐eye movement (REM) and in total sleep: r = 0.48, p = 0.005, and r = 0.44, p = 0.01), were significantly associated with total WMH volume. Similar relationships were found with time spent below 90% and 80% oxygen saturation (Kendall’s tau = 0.33, p = 0.02 and tau = 0.275, p = 0.03). These relationships survived adjustment for sex, age, and hyperlipidemia and/or hypertension medication at time of PSG. Global WMH volume was also negatively associated with overnight memory retention (r = ‐0.38, p = 0.03).

Conclusions

These findings suggest that hypoxemia severity, compared to sleep fragmentation, are more strongly associated with global WMH volume. As WMH volume was associated with overnight memory retention, this may suggest a pathway in which OSA increases WMH, which is subsequently associated with tau burden, worsening sleep‐dependent memory.
Validation of early‐frame 18F‐FDG PET for CBF quantification: Comparison to simultaneous eASL measurements in memory patients
Authors: Fettahoglu Ates , Zhao Moss , Chen Kevin , Khalighi Mehdi , Zeineh Michael , Mormino Elizabeth C. , Moseley Michael , Zaharchuk Greg
Published: December 2023

Background

This study aimed to validate early [18F]‐FDG (eFDG) imaging for the quantification of cerebral blood flow (CBF), enabling dual‐marker imaging of perfusion and metabolism with a single tracer.

Method

19 participants with memory concerns underwent simultaneous [18F]‐FDG PET and multi delay pseudo‐continuous arterial spin labeling (eASL) MR imaging on a hybrid 3T PET/MRI scanner. eFDG‐CBF maps were generated from the first 30s, 60s, 120s and 300s after injection, and measurements were compared to ASL‐CBF using voxel‐wise cross correlation and concordance correlation for 7 regions derived from the MNI‐structural atlas.

Result

Highest voxel‐wise cross‐correlation to ASL‐CBF maps were reported for 300s (5 min) eFDG (r = 0.77).Concordance correlation (CC) values were strong in all ROIs, ranging from (CC = 0.88) to (CC = 0.65) in temporal and occipital regions respectively. Mean of measurements in all ROIs were in good agreement between eFDG and ASL CBF maps, with a reported voxel‐wise mean absolute error of ±6.73 ml/100g/min between two maps.

Conclusion

By simultaneous measurement of hemodynamics across modalities with a TOF‐enabled PET/MRI, we were able to demonstrate that eFDG PET is a reliable measure in mapping CBF based on strong inter‐modality correlation with ASL‐CBF, irrespective of pathophysiological variations in memory patients.
Trends in the prevalence of dementia in LMIC: findings from 10/66 studies in Latin America and the Caribbean.
Authors: Llibre‐Rodriguez Juan J. , Acosta Daysi , Guerra Mariella , Sosa‐Ortiz Ana Luisa , Velazquez Ivonne Z. Jimenez , Salas Aquiles , Llibre‐Guerra Jorge J , Prince Martin J ,   10/66 Dementia Research Group
Published: December 2023

Background

Population ageing will lead to a dramatic increase in dementia prevalence globally. Recent evidence suggest a decline in dementia incidence in High Income Countries due to increasing education levels and improvements in cardiovascular health. Although, most of the increase will occur in low and middle‐income countries (LMICs), there are no recent estimates of dementia prevalence and incidence in LMICs. The present study aimed to examine new trends on dementia prevalence and incidence in Latin‐America and associations of socioeconomic determinants and cardiovascular risk factors.

Method

Sample size included older adults from Latin America (Cuba, Dominican Republic [DR], Puerto Rico [PR], and Mexico) drawn from the 10/66 Dementia Research Group study. We compare wave 1 (2003‐2006) with wave 3 (2016‐2019) of 10/66 studies. The main outcome was dementia prevalence relative to previous waves. Dementia diagnosis was determined according to 10/66 dementia criteria. All the 10/66 waves used the same standardized assessments and protocols.

Result

Dementia prevalence is stable Cuba, standardized dementia prevalence rates was 12.4% in wave I and 10.1% in wave III. Relative to wave I, Dominican Republic (wave I 11.5% vs wave II 13.6%), Peru (wave I 9.2% vs wave II 16.8%) and Mexico (wave 1 8.3% vs wave 2 17.1%) experience a significant increase in dementia prevalence. Despite, improvements in levels of education, increases in dementia prevalence were associated with higher rates of cardiovascular disease and cardiovascular risk factors, including diabetes, hypertension, obesity and heart disease in the later‐born cohorts. Self‐reported stroke is also rising.

Conclusion

The prevalence of dementia in the older Latin American and Caribbean population is high and increasing relative to the previous decade. These findings may inform health promotion efforts within dementia national plans adopted recently in some Latin American countries
Falls Risk Profile in Community Dwelling Adults with Moderate‐Severe Cognitive Impairment
Authors: Ho Yun Ying , Chong Elizabeth Gar Mit
Published: December 2023

Introduction

It is well established that older adults with cognitive impairment are more likely to fall. Injurious falls lead to functional decline and higher level of mortality. The Centers for Disease Control and Prevention, USA further concluded 20% falls resulted in serious injuries which were either fractures and/or head injuries.

Methodology

This paper aimed to evaluate the relationship between characteristics of fallers with moderate cognitive impairment and osteoporosis. A single center cross sectional study with universal sampling was performed for all patients who attended the transdisciplinary falls clinic in a large tertiary center in Klang Valley from January 2015 till January 2023. Anonymised data was collected from the existing falls database. Subjects with MMSE score 0‐18 were categorised as having moderate‐severe cognitive impairment.

Results

During the study period, a total of 185 older adults were assessed with 96 females (51.9%) and 35 (18.9%) with moderate‐severe cognitive impairment. They were all community dwellers. All those with moderate‐severe cognitive impairment had previous history of falls. 91.3% subjects with mild or no cognitive impairment had fallen before. Those who stayed alone (0 out of 21 subjects) were less likely to have moderate‐severe cognitive impairment (p value 0.037). Subjects with moderate‐severe cognitive impairment had lower hip T‐score (mean ‐2.23, SD1.93, p = 0.026), Mechanisms were more likely due to slipping (25.7%, p = 0.03) and less likely because of losing balance (22.9%, p = 0.006). The Berg Balance Scores were numerically higher 42.2 (SD32.3) but did not achieve statistical significance (p = 0.652). These fallers were less likely to fall out of home (11.4%, p = 0.017). 34.3% fallers with moderate‐severe cognitive impairment required assistance to ambulate (p = 0.034). There was no difference for the following parameters: age, gender, ethinicity, multi‐morbidities, polypharmacy, sensory impairment, history of falls, recurrent falls, frequencies of any injuries sustained including fractures or intracranial hemorrhage, admission for falls and presence of osteoporosis.

Conclusion

This study suggested that community dwelling older adults with moderate‐severe cognitive impairment had similar falls risk profile comparing to their counterparts. Clinicians should be more vigilant in screening for falls risk in this population and be proactive in managing their bone health.
The association between gut microbiota and postoperative delirium in patients
Authors: Zhang Yiying
Published: December 2023

Background

Postoperative delirium is one of the most common postoperative complications in older patients. Its pathogenesis and biomarkers, however, remain largely undetermined. Majority of human microbiota is gut microbiota and gut microbiota has been shown to regulate brain function. Therefore, this study aimed to determine the association between gut microbiota and postoperative delirium in patients.

Method

Of 220 patients (65 years old or older) who had a knee replacement, hip replacement, or laminectomy under general or spinal anesthesia, 86 participants were included in the data analysis. The incidence (primary outcome) and severity of postoperative delirium was assessed for two days. Fecal swabs were collected from participants immediately after surgery. The 16S rRNA gene sequencing was used to assess gut microbiota.

Result

Using principal component analyses along with a literature review to identify biologically plausible mechanisms, and three bacterials were studied for their associations with postoperative delirium. Of the 86 participants [age 71.0 (69.0‐76.0, 25%‐75% percentile of quartile), 53% female], ten (12%) developed postoperative delirium. Postoperative gut bacteria Parabacteroides distasonis (Odds Ratio [OR] 2.13, 95% Confidence Interval (CI): 1.09 ‐ 4.17, P = 0.026) was associated with postoperative delirium after adjusting for age and sex. The association between delirium and both Prevotella (OR: 0.59, 95% CI: 0.33 – 1.04, P = 0.067) and Collinsella (OR: 0.57, 95% CI: 0.27 – 1.24, P = 0.158) did not meet statistical significance.

Conclusion

These findings suggest that postoperative gut microbiota (e.g., Parabacteroides distasonis) may serve as biomarkers in the pathogenesis of postoperative delirium, pending confirmative studies.
Psychotropic Medications in People with Alzheimer’s Disease in Care Homes
Authors: Alotaibi Talal A , Smith Mathew , Lane Emma , Kidd Emma J
Published: December 2023

Introduction

Depression in Alzheimer’s disease (AD) is difficult to treat and our preliminary data in care homes, captured from electronic medicines administration records (eMAR) suggested that residents with AD were receiving multiple psychotropic drugs. We are investigating the psychotropic burden of AD residents to determine whether treatment is appropriate. We report here demographic characteristics of all care home residents.

Methods

Secondary cross‐sectional, pseudonymised data for residents in care homes were collected by eMAR from 2014‐2020. SQLPRO Studio was used to interrogate the database and mediations were classified using the BNF. Residents with archived records, aged >105 years, with unclear gender or stopped medication status were excluded.

Results

9060 residents living in 310 care homes across the UK were included. 29% and 71% were male and female, respectively. 38% were ‘youngest‐old’ (65 ‐ 85 years) with 62% ‘oldest‐old’ (85 ‐ 105 years). The mean number of active medications per resident was 10.36 (SD 4.9). ‘Youngest‐old’ males and females had 11.11 (SD 5.2) and 10.54 (SD 5.1) active medications, respectively versus 10.56 (SD 4.9) and 9.99 (SD 4.7) active medications in the Oldest‐old.

The top three classes of active mediations were for the nervous (28%), gastrointestinal (19%) and cardiovascular (14%) systems. For the nervous system, the largest classes were analgesics (44%) and antidepressants (17%).

Residents administered psychotropic medications were 30.5% male and 69.5% female with 44.5% for ‘youngest‐old’ and 55.5% for ‘oldest‐old’ residents. The medications comprised antidepressants (48.7%), antipsychotics (13.8%) and anxiolytics (6.5%). The mean number of active psychotropic medications per resident was 1.54 (SD 0.794).

Conclusions

Most care home residents were female and ‘oldest‐old’ agreeing with the 2011 census and showing the study population is representative of care home residents. Nervous system medications were the largest class with antidepressants the highest psychotropic class and largely prescribed to the female ‘oldest‐old’.
The potential cost‐effectiveness of roflumilast drug treatment in mild cognitive impairment
Authors: Handels Ron , Grimm Sabine , Blokland Arjan , Possemis Nina , Ramakers Inez H.G.B. , Sambeth Anke , Verhey Frans R.J. , Vos Stephanie J. B. , Joore Manuela , Prickaerts Jos , Jönsson Linus
Published: December 2023

Background

Evidence is needed on the value of new (pharmacological) health technologies in their early stage of development, to support stakeholders (industry, regulators, payers, and health care providers) in decision‐making linked to their further development and introduction in routine care. Early health‐technology assessment supports stakeholders by providing insight into the size and uncertainty of the expected benefits new technologies may have. This can facilitate early guidance on positioning in clinical practice and research recommendations. Our objective was to provide a pragmatic example of the potential cost‐effectiveness of roflumilast treatment in addition to usual care versus usual care alone if prevention of progression to dementia is in part realized in a population of patients diagnosed with a mild cognitive impairment (MCI) at a memory clinic.

Method

The IPECAD open‐source decision‐analytic model was used to simulate the natural disease progression of MCI and dementia and estimate the quality‐adjusted life years (QALYs) and care costs, comparing roflumilast treatment added to usual care with usual care alone. In this model roflumilast proof of concept evidence on a visual 30‐word verbal learning test (0.39 z‐score) was translated using a published risk equation model to a relative risk of 0.93 for developing dementia. The treatment was assumed symptomatic with no effect on mortality.

Result

More lifeyears were spent in MCI in the roflumilast strategy compared with usual care, with 0.2 increment lifeyears (95%CI: 0.0 to 0.6) (see figure 1), and 0.04 incremental lifetime QALYs (95%CI: 0.00 to 0.11) and k€1.3 adjusted societal costs (95%CI: ‐6.3 to 5.5) (see figure 2). This resulted in an incremental cost‐effectiveness ratio of k€34 per QALY (see table 1). Roflumilast was estimated to have a 37% probability of being cost‐effective (net health benefit 95% interval ‐0.27 to 0.42), with uncertainty mainly driven by extrapolating the word learning surrogate outcome to the patient‐relevant outcome of dementia onset, and the efficacy estimate (see figure 3).

Conclusion

The potential cost‐effectiveness of roflumilast treatment is uncertain, driven by uncertainty in treatment efficacy and extrapolation to postponing dementia onset. We believe the results indicate a potential for roflumilast and provide several recommendations to consider investing in its future research.
Longitudinal free‐water changes in dementia with Lewy bodies
Authors: Chiu Shannon Y , Chen Robin , Wang Wei‐en , Armstrong Melissa J , Boeve Brad F. , Kantarci Kejal , Vaillancourt David
Published: December 2023

Background

Diffusion‐weighted MRI (dMRI) examines tissue microstructure integrity and white matter pathways in vivo. Prior dementia with Lewy bodies (DLB) studies focused on white matter or voxel‐based techniques. Less is known about longitudinal white and grey matter microstructural changes in DLB. We aimed to characterize longitudinal diffusion microstructural changes in individuals with DLB.

Method

dMRI scans were collected on individuals with DLB from the Mayo Clinic Longitudinal Imaging Biomarkers of DLB Program. Demographics, clinical evaluations and MRI were collected at baseline, and 12‐ or 24‐months. Free water (FW) and FW‐corrected fractional anisotropy (FAT) were analyzed in grey and white matter using 122 bilateral template regions and tracts of interest from the Mayo Clinic Adult Lifespan Template. Primary outcomes were differences in FW and FAT between baseline and 12‐ or 24‐months.

Result

We identified 23 individuals with DLB or mild cognitive impairment with Lewy bodies (MCI‐LB) from baseline to 12‐months [mean age 69.3 years (SD 9.5); 95.8% male], and 16 individuals from baseline to 24‐months [mean age 67.5 years (SD 9.3); 100% male]. Participants at both time‐points showed worsening in Montreal Cognitive Assessment and Movement Disorders Society Unified Parkinson’s Disease Rating Scale motor scores (p<0.05). We found significant differences in FW, but not FAT, from baseline to 12‐months. Significant increases in FW at both time‐points compared to baseline were observed in the insula, putamen, parahippocampal, and rolandic operculum regions (pfdr<0.05). We found additional more widespread microstructural changes from baseline to 24‐months, with increased FW in the amygdala, entorhinal, mid and posterior cingulum, inferior frontal, hippocampal, pallidum, precuneus and retrosplenial regions (pfdr<0.05). We found decreased FAT from baseline to 24‐months in the cerebellar and superior occipital regions (pfdr<0.01).

Conclusion

Longer follow‐up at 24‐months identified broader networks of free water changes in individuals with DLB. Results support dMRI as a promising, non‐invasive tool to track disease progression in DLB. More investigation is needed to evaluate the relationship of microstructural changes with clinical progression in DLB.
New polygenic risk score for Alzheimer’s disease impacts states and functions in iPSC‐derived microglia.
Authors: Therrien Martine , Atkeson Trevor , Meyer Daniel , Ghosh Sulagna , Turley Patrick , Stevens Beth
Published: December 2023

Background

Recent genetics studies for Alzheimer’s disease have identified multiple risk variants affecting amyloid processing, immune response, lipid transport, and endocytosis, among others 1. More than half the risk genes associated with late‐onset AD are selectively expressed in microglia and peripheral myeloid cells. Yet, we know little about the underlying biology or how myeloid cells contribute to AD pathogenesis.

Method

To gain insights into the broad impact of genetics on microglia, we selected 50 cell lines from the CIRM biobank with variable APOE genotypes and polygenic risk scores (PRS). Building on our in vitro platform that recapitulates microglia states in vitro 2, we used villages 3, or pooled culture, to differentiate these lines into microglia and assessed key microglia functions, transcriptional profiles, and response to various perturbations.

Result

Cell villages allow us to compare phenotypes across lines with little technical variability robustly. Our data determined functional phenotypes that were altered by PRS and others that were affected by APOE genotypes. Moreover, quantitative trait locus (QTL) analysis identified new variants affecting phagocytosis, proliferation, and response to lipids. Finally, single‐cell RNA sequencing of our village pinpointed key microglia pathways altered between high and low PRS individuals.

Conclusion

Cell village allows for the characterization of up to hundreds of cell lines while minimizing technical variability allowing us to identify phenotypes dysregulated across various genetic backgrounds. Our data pinpointed the impact of a novel Alzheimer’s disease PRS on microglia states and functions and identified new variants affecting microglia functions.

1. Sims, R., Hill, M. & Williams, J. Nat Neurosci
23, 311‐322 (2020). 2. Dolan, M.‐J. et al. Biorxiv 2022.05.02.490100 (2022) https://doi.org/10.1101/2022.05.02.490100. 3. Wells, M. F. et al. Biorxiv 2021.11.08.467815 (2021) https://doi.org/10.1101/2021.11.08.467815.
Exploring cultural differences in the understanding of Alzheimer’s Disease and related dementias among Alaska Natives and providers in Alaska
Authors: Kim Steffi M , Lewis Jordan P.
Published: December 2023

Background

The proportion of the Native population aged 65+ is projected to increase between 2015 and 2045, from 7‐12%, and informal caregivers and health care providers are ill‐prepared to meet the demand of Alzheimer’s Disease and related disorders (ADRD). There is an increasing urgency to better understand Alaska Native views of ADRD.

Method

Guided by Kleinman’s explanatory model of illness, a qualitative, research design was utilized to gather data on experiences with ADRD. 21 interviews with Alaska Native caregivers and 12 interviews with health care providers in rural and urban communities were completed. Using Nvivo qualitative software, thematic analysis was used to obtain cultural perspectives on ADRD. This study was approved by the University and tribal review boards.

Result

Many Alaska Natives view ADRD as a natural part of the aging process, resulting in not always seeking medical care. Caregivers challenges included family denial, exhaustion and isolation, and family distancing themselves due to fear and limited understanding of ADRD. Caregiving benefits included spending time with older adult, learning family history, and sharing experiences with other caregivers. Healthcare provider challenges included rigidity of the healthcare system, no research on Alaska Natives, limited health literacy, limited community resources, and no knowledge of Alaska Native views of ADRD.

Conclusion

Understanding the cultural underpinnings of ADRD provides insight into how health care providers can integrate cultural beliefs into treatment to improve the processes of care that may mitigate the impact of ADRD on individuals and families. Culturally‐responsive education and training about ADRD is crucial to connecting Alaska Natives with ADRD to care that can assist them in aging more comfortably