bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual Respite for Family Caregivers
Authors: Washington Tiffany R , Rapowitz Jennifer
Published: December 2023

Background

There are over 11 million family caregivers to individuals living with Alzheimer’s in the U.S. The risk of caregiver burden and the inaccessibility of institutional respite create a need for in‐home respite programs. This proof of concept study examined the feasibility of an in‐home virtual respite program.

Method

Family caregivers of individuals with mild dementia received up to six student delivered in‐home virtual respite visits over two months. Semi‐structured interviews were conducted with family caregivers and student participants following the visits. The qualitative data were analyzed using thematic analysis with three coders.

Result

Family caregivers reported that the virtual respite program allowed time to engage in self‐care activities such as rest, exercise, and social interaction.

Conclusion

This novel intervention freed time for family caregivers to receive respite in a virtual format. A future randomized trial is needed to estimate the effect of the intervention on psychosocial and clinical outcomes.
Contribution of a dysfunctional variant of ALDH4A1 to Alzheimer’s Disease pathology through altered metabolism and mitochondrial impairment
Authors: Kraemer Benjamin R , Mochly‐Rosen Daria
Published: December 2023

Background

Aldehyde dehydrogenases (ALDH) are enzymes which oxidize toxic aldehydic species into carboxylates. ALDH4A1 is a mitochondrial, NAD+‐dependent, dimeric enzyme and oxidizes the toxic aldehyde glutamic‐g‐semialdehyde (GSA) to glutamate. ALDH4A1 lies at the nexus of proline and arginine metabolism, the TCA cycle, and mitochondrial health (Fig. 1). The substrate of ALDH4A1, GSA, inactivates vitamin B6 (Farrant et al., 2001), an essential cofactor for amino acid and neurotransmitter biosynthesis. Toxic aldehydes like 4‐hydroxynonenal (4‐HNE), are elevated in Alzheimer’s Disease (AD) patients (Markesbery & Lovell, 1998) and promote amyloid‐b aggregation (Siegel et al., 2007). A recent genetic analysis identified a missense variant of ALDH4A1 as a risk factor for Late Onset Alzheimer’s Disease (LOAD) (Wang et al., 2015). Our previous analysis found that ALDH4A1 is an essential enzyme with no common loss of function variants (Chen et al., 2021). Our work elucidates the contribution of ALDH4A1 to AD pathology.

Method

Recombinant protein was characterized to determine changes in protein activity and stability. The AD risk factor mutation was knocked‐in to the endogenous locus of induced pluripotent cells to monitor mitochondrial health, metabolism, and AD biomarkers. Mouse embryonic fibroblasts that do not express ALDH4A1 were used to monitor protein stability in cellulo.

Result

The AD associated variant of ALDH4A1 has decreased activity compared to wildtype (WT) (Fig. 2). ALDH4A1 can oxidize the toxic AD‐associated aldehyde 4‐HNE, and the variant has 50% of the activity of WT with 4‐HNE (Fig. 2). The variant enzyme is less stable in cellulo; variant ALDH4A1 is degraded within a few hours compared to WT that remains stable up to 24 hours. Knock‐in cells accumulate 25% more extracellular proline, and show a trend towards increased intracellular proline, indicating faulty proline metabolism in cells expressing the AD‐associated mutant ALDH4A1.

Conclusion

ALDH4A1 oxidizes AD associated aldehydes (i.e., 4‐HNE) in addition to its known substrate. The AD‐associated variant of ALDH4A1 is less catalytically active and less stable than the WT enzyme. Cells expressing this variant have dysregulated proline metabolism. These data indicate that ALDH4A1 variants may contribute to AD through altered metabolism and increased aldehydic load from dysregulated protein activity and stability.
Time spent in outdoor light is associated with the risk of dementia: a prospective cohort study of 362094 participants
Authors: Ma Lingzhi
Published: December 2023

Background

Few epidemiological studies in the adult population related these outcomes to daytime sunlight exposure.

Method

Data were from a prospective cohort of 362094 UK Biobank participants. Questionnaire survey was conducted to investigate how many hours the participants spent outdoors on typical summer and winter days. Restricted cubic spline (RCS) was performed to explore the potential nonlinear relationship between sunlight exposure and the risk of dementia.

Result

More specifically, we prefer to describe this nonlinear relationship with J shape, the lowest risk at three change points (1.5 hours/day on average, 2 hours/day in summer, and 1 hour/day in winter). Since for sunlight exposure, a marked increase in risk was observed at low exposure, but a relatively slow elevation in risk at higher exposure.

Conclusion

There is a J‐shaped correlation between outdoor sunlight exposure time and dementia risk.
Population‐based Dementia Identification and Care Coordination: The CS CARES Program
Authors: Tan Zaldy S , Qureshi Nabeel , Kremen Sarah , Rhinehart Deana , Gatmaitan Dyane , Spivack Erica , Guinto Augustine , Sicotte Nancy
Published: December 2023

Background

Alzheimer’s disease and related dementias (ADRD) afflict over five million persons in the U.S., and persons living with dementia (PLWD) have been shown to receive poor quality care and experience worse health outcomes compared to those without ADRD. While dementia care programs have been shown to improve these outcomes, to date, the effects have not been studied in a value‐based Medicare population.

Methods

In a large multi‐specialty medical group practice, we identified patients enrolled in a value‐based insurance program (Medicare Advantage) using the EPIC electronic health record (EHR). Patients were eligible to enroll in a care coordination program if they had an ICD‐10 diagnosis of ADRD in the EHR problem list and/or past medical history, or currently taking an FDA‐approved medication for ADRD. We invited eligible patients to enroll in the CARES dementia care program and additionally included patients with ADRD who have a primary care provider in the health system. A study‐assigned nurse practitioner (NP) identified the patient’s medical, behavioral, and psychosocial needs using the novel CEDARS‐6 dementia care tool to formulate and share a care plan with the patient’s primary care provider. Regular check‐in calls were scheduled, and care plans were updated based on patient’s status. To evaluate patient and caregiver baseline health status, we assessed patient behavior (NPI‐Q), caregiver stress [Modified Caregiver Strain Index (MCSI)], and caregiver depression (PHQ‐9).

Results

We enrolled 195 (33.1%) of eligible patients, with non‐responders to the invitation accounting for the majority (75%) of non‐enrollees. The average age of enrollees was 81.3 (SD = 9.16) years old, 64.6% were female, and 81.2% identified English as their primary language. Based on caregiver report, patients scored an average NPI‐Q Severity score of 10.40 (6.87), and an average NPI‐Q Distress score of 13.80 (10.54). Caregivers scored an average PHQ‐9 score of 5.65 (5.28) and MCSI score of 10.62 (7.01).

Conclusion

PLWD proactively enrolled in a dementia care program have high baseline rates of behavioral issues and their caregivers have elevated depression and stress scores. It is important to track the longitudinal effects of the CARES dementia program on these measures.
Call and response: Ethnomusicological methods to awaken specific memories with targeted songs encoded in neuronal populations of a dementia patient
Authors: Pillay Jayendran
Published: December 2023

This study collaborates with a fellow expert ethnomusicologist Sean Williams to trigger specific contextual memories associated with songs of her mother Julian Williams, born in 1932, and currently struggling with the early stages of dementia. The goal was to ascertain the success rate of a one‐to‐one correspondence type: The use of targeted, known songs of the dementia patient as a means to trigger the patient’s contextual memories.

By adopting a methodology in Ethnomusicology involving the autobiography of one’s music history and their corresponding memories of the patient Julian Williams, I set up the experiment for Sean Williams to conduct. Dividing the study into discrete music time periods (infancy, childhood, teenager, young adult, older adult), I asked Sean Williams to choose specific songs with specific memories to the patient to be sung. The memory responses of the patient on video were then recorded.

Each of those songs had deep levels of recognition by the Alzheimer’s patient, as evidenced in her singing with some memories (lyrics and contextual environment) stronger than than others. The fact that there is some autobiographical recall, despite a weakened sense of time and space after the onset of Alzheimer’s, suggests there may be use for this technique in dementia care. Of note, is the fun‐filled disposition of the participants during the recording of the singing. That speaks to a higher quality of life one could expect by using music as a memory‐recall and time‐ travel companion.

This single case study needs to be broadened into a larger‐scale experiment involving many participants from different cultures to ascertain the use of individualized targeted songs to awaken specific memories of the dementia patients. In the area of dementia care, this approach also makes it possible for families to participate actively since the songs will probably be known to them as well.
TeleCARE: A telehealth group to teach dementia caregivers how to manage neuropsychiatric symptoms
Authors: Shirk Steven , Moo Lauren R. , McLaren Jaye E. , Pugh Kendra , Nguyen Andrew H. , O'Connor Maureen K.
Published: December 2023

Background

Negative outcomes associated with caring for a loved one with ADRD include increases in caregiver depression, anxiety, and burden often due to managing neuropsychiatric symptoms (NPS). CARE is an in‐person, group‐based behavioral intervention that teaches caregivers specific skills to manage the NPS that are common in ADRD. Prior to the COVID‐19 pandemic, we were funded to adapt the CARE program to a virtual format (TeleCARE) in order to improve access to specialized services for caregivers with barriers to in‐person care. The impact of COVID‐19 further underscored the importance of telehealth interventions for caregivers.

Method

Twenty caregivers participated in TeleCARE using the Cisco Webex platform. Caregivers were predominately female (80%), spouses (80%), ranging in age from 35‐88 (M = 70.8). The CDR‐Sum of Boxes was administered to measure dementia severity of the care recipients with a mean of 11.1 (moderate dementia). Data were collected at baseline and immediately following completion of the 8‐week group intervention.

Result

Eighty‐five percent of caregivers had a better understanding of NPS, and 90% of caregivers felt TeleCARE helped them take better care of the person with dementia and improved their ability to manage caregiving. Caregivers reported reduced depression and anxiety following the intervention (BDI: M = 9.6 vs M = 7.8; BAI: M = 8.7 vs. M = 6.8). They also reported increases in Positive Aspects of Caregiving (M = 33.2 vs. M = 35.3) and Meaning and Purpose in Life (M = 53.7 vs. M = 55.3). They reported little reduction in distress related specifically to NPS (M = 20.3 vs. M = 19.7).

Conclusion

The TeleCARE adaptation was successful, with caregivers reporting improvements in understanding of NPS, caregiver depression and anxiety, ability to care for their loved one, and management of caregiving tasks. Even with the return to in‐person care options after the peak of the COVID‐19 pandemic, the nature of dementia caregiving often does not allow caregivers to easily leave home to join in‐person programs. Geographical distance, time, and money spent finding care for loved ones can be barriers to participation. Our results suggest TeleCARE may serve as an effective option to increase access to group caregiver education and support.
Biological sex and vessel specific relationships between cerebral pulsatility and white matter hyperintensities: a 4D flow MRI study
Authors: Moir M. Erin , Fico Brandon G. , Loggie Nicole A. , Gaynor‐Metzinger Sarean H.A. , Norby Alexander M. , Howery Anna J. , Rivera‐Rivera Leonardo A. , Eisenmenger Laura B. , Wieben Oliver , Johnson Sterling C , Barnes Jill N.
Published: December 2023

Background

Brain vascular dysfunction is a contributing factor to the increased risk of Alzheimer’s disease with advancing age. Cerebral pulsatility represents a marker of vascular function that quantifies fluctuations in blood flow within each cardiac cycle in the cerebral arteries. Increases in cerebral pulsatility may contribute to structural damage in the brain such as white matter hyperintensities (WMH). Additionally, biological sex differences are apparent in brain vascular function and Alzheimer’s disease risk. As such, this research aimed to determine associations between cerebral pulsatility and WMH and evaluate the influence of sex. This research tested the hypothesis that elevated cerebral pulsatility is associated with higher WMH, and that the associations are sex‐specific.

Method

407 cognitively healthy middle‐aged and older adults (45‐87 years of age; 271 females) completed magnetic resonance imaging (MRI) performed on a 3T MRI scanner. WMH volumes were evaluated from T2 fluid‐attenuated inversion retention (FLAIR) images, while cerebral pulsatility index (PI) was evaluated in multiple intracranial arteries from 4D flow MRI. WMH fraction was calculated as the cubic root of WMH volume relative to intracranial volume.

Result

PI in the vertebral arteries (VA) and basilar artery was positively associated with WMH fraction in females only (all female P≤0.01, all male P≥0.20). In contrast, PI in the internal carotid arteries (ICA) and middle cerebral arteries (MCA) was positively associated with WMH fraction in both sexes (all P≤0.01). However, the relationship between WMH fraction and PI in the MCA differed by sex such that the slope of the relationship was stronger in males than females (all P≤0.03). For example, higher right MCA PI was associated with greater WMH fraction in males (β = 0.39±0.09 a.u., R2 = 0.13) compared with females (β = 0.18±0.05 a.u., R2 = 0.05).

Conclusion

These data suggest that, among cognitively healthy middle‐aged and older adults, elevated cerebral pulsatility is linked to greater WMH. However, the associations are sex‐ and vessel‐specific which may contribute to sex‐specific trajectories in Alzheimer’s disease with advancing age. The present results support the idea that elevated cerebral pulsatility contributes to structural alterations in the brain and thus reducing cerebral pulsatility may represent a promising target for mitigating cognitive decline.
Investigating cognitive performance of healthy older adults using phase synchrony analyses of EEG signals
Authors: Nemati Samaneh , Newman‐Norlund Roger , Newman‐Norlund Sarah , Fridriksson Julius
Published: December 2023

Background

Aging is a physiological process considered as a major risk factor for most irreversible neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Moreover, it is highly associated with decline in attention, memory, communication skills and many other cognitive functions as well as an overall delay in cognitive information processing in aging individuals free of any neurodegenerative diseases. Although much research has been done on the human brain in clinical cohorts, fewer studies have investigated the impact of age in healthy aging individuals. However, results of neuroimaging studies indicate that healthy aging is accompanied by significant structural and functional changes in the brain. This study uses EEG coherence and phase synchrony measures to investigate the relationship between the neural connectivity in the human brain and cognitive scores from the Montreal Cognitive Assessment (MoCA) in healthy older adults.

Method

75 participants aged between 60‐80 (M = 66.78, SD = 6.98) were recruited as part of the Aging Brain Cohort dataset at the University of South Carolina (ABC@UofSC). Resting‐state EEG signals were recorded from 128 electrodes using the Brain Vision actiCAP slim electrode layout with 500 Hz sampling frequency rate while participants were sitting quietly in a room using the Acti‐CHAMP EEG plus system. After preprocessing and denoising EEG signals, phase synchrony measure between each pair of electrodes was calculated for all frequency bands (delta, theta, alpha, gamma). Finally, a univariate general linear model (GLM) analysis was used to identify significant relationships between resting‐state functional connectivity indexed by phase synchrony and cognitive scores assessed by MoCA test while controlling for participants’ chronological age and gender.

Results

Our preliminary results revealed a significant association between cognitive scores and resting‐state functional connectivity of several brain electrodes in frontal, temporal, and parietal areas in high frequency alpha and beta bands.

Conclusion

Our results provide evidence that phase synchrony, a statistical measure of correlation between signals from electrodes spatially separated on the human scalp, could provide reliable biomarkers of cognitive performance of individuals in pre‐clinical disease states. This could enhance the clinicians’ ability to make early diagnosis of cognitive decline in older adults.
Snapshot of utilization of mobile research units for community screening with an emphasis in reaching previously underserved and underrepresented communities strategically across Central Florida
Authors: Cassidy Stephanie , Torres Sandra , Baez‐Torres Sheila , Lenox Brandon , Stanton Sean
Published: December 2023

Background

Increasing diversity in clinical trials requires intentionality and strategic planning. Traditional recruitment methods do not address barriers resulting in statistics supporting the majority of clinical trial participants being Caucasian, Non‐Hispanic males1. Identified barriers for these diverse populations in research include lack of knowledge on clinical trials, transportation, language and trust2.

Effective methods to reach diverse communities require an “out of the box” thinking, intentionality, and creativity. By utilizing a Mobile Research Unit and bringing research to participants, sites are able to breakdown some of these barriers to better serve historically underserved and underrepresented populations.

Method

A Mobile Research Unit was utilized in underserved and underrepresented areas which the site had built rapport with. During the time the Mobile Research Unit is in use, site staff engaged with the community by educating participants and by doing a hands‐on meaningful activity. Memory and/or blood base biomarkers were administered to patients who qualified.

Result

171 participants were screened for studies over a period of 4 months utilizing a mobile research unit. 42% of those screened are from diverse populations. 59% of those who screened were identified to be at risk and eligible for further screening.

Conclusion

By breaking down some of the identified barriers, K2 was able to achieve better outcomes than what is typically seen in research of diverse populations. Utilizing the Mobile Research Unit and bringing research to participants allowed K2 to strengthen community connections and take some of the burden off participants. K2 will continue to support initiatives in enrolling diverse populations and employing tactics learned while supporting the Mobile Research Unit.

References:

1. Ma, M. A., Gutiérrez, D. E., Frausto, J. M., & Al‐Delaimy, W. K. (2021). Minority representation in clinical trials in the United States. Mayo Clinic Proceedings, 96(1), 264‐266. https://doi.org/10.1016/j.mayocp.2020.10.027

2. Luther T. Clark, Laurence Watkins, Ileana L. Piña, Mary Elmer, Ola Akinboboye, Millicent Gorham, Brenda Jamerson, Cassandra McCullough, Christine Pierre, Adam B. Polis, Gary Puckrein, Jeanne M. Regnante, Increasing Diversity in Clinical Trials: Overcoming Critical Barriers, Current Problems in Cardiology, Volume 44, Issue 5, 2019, Pages 148‐172, ISSN 0146‐2806, https://doi.org/10.1016/j.cpcardiol.2018.11.002.
Identify Alzheimer’s disease subtypes and markers from multi‐omic data of human brain and blood with a subspace merging algorithm
Authors: Song Ziyan , Huang Xiaoqing , Huang Kun , Zhang Jie
Published: December 2023

Background

Alzheimer’s disease (AD) is a highly heterogeneous disease with different disease trajectory, brain pathological changes, and risk factors. Identifying subtypes of AD can have greatly impact AD diagnosis, treatment, and disease management. Our goal is to identify subtypes of AD by integrating multiple types of omics data from AD patients’ brain samples and blood samples.

Method

We applied a subspace merging algorithm on AD patient brain samples with matched transcriptomic, DNA methylation, and proteomics data collected from the ROSMAP study. This algorithm merges patient graphs generated from these three datasets on a Grassmann manifold followed by spectral clustering. Differential gene expression and pathway analysis were applied to establish the gene signatures between the subtypes (patient clusters) and to the transcriptomic data of the peripheral blood monocyte (PBMC) from the matching patients to identify possible blood markers.

Result

Our analysis identified two patient clusters between which the cognitive test scores or the degree of AD pathology are significantly different. Differentially expressed genes between the two groups were identified from both brain and blood samples. Gene set enrichment analysis identified a group of genes significantly enriched with synaptic functions in the brain samples. The Ingenuity Pathway Analysis was used to examine any connections between the significantly differentially expressed genes in the brain samples with the ones identified from the PBMC samples. The low density lipoprotein receptor (LDLR) gene, which was an APOE receptor observed from the blood sample is connected with 12 genes from the brain sample. The results suggested that LDLR could be a novel blood biomarker for AD subtyping.

Conclusion

The subspace merging algorithm integrated multimodal omics data from the patients and successfully identified two clusters with distinct clinical progression. Differential expression analysis identified 388 significant genes from the brain samples and 18 from the PBMC samples. The pathway analysis indicated that LDLR could be a novel blood biomarker for AD subtyping. Future work will focus on validating LDLR as a candidate blood marker for AD subtyping using other public datasets with similar study design. The clinical relevance and molecular mechanism basis for the findings will also be investigated.
Social determinants of health and medical factors on brain health in Colombian underserved populations
Authors: Santamaria‐Garcia Hernando , Moguilner Sebastian , Hernandez Hernan , Rodriguez‐Villagra Odir , Ibanez Agustin
Published: December 2023

Background

Global initiatives call for further understanding of the impact of inequity on aging across underserved populations. Previous research in LMICs presents limitations in assessing combined sources of inequity and outcomes (i.e., cognition and functionality). In this study, we assessed how social determinants of health (SDH), cardiometabolic factors (CMF), and other medical/social factors predict cognition and functionality in an aging Colombian population.

Method

We ran a cross‐sectional study that combined theory‐ (structural equation models and population attributable risk scores), and data‐driven (machine learning) approaches in a population‐based study (N = 23,694; M = 69.8 years) to assess the best predictors of cognition and functionality.

Result

We found that a combination of SDH and CMF accurately predicted cognition and functionality, although SDH was the stronger predictor. Cognition was predicted with the highest accuracy by SDH, followed by demographics, CMF, and other factors. A combination of SDH, age, CMF, and additional physical/psychological factors were the best predictors of functional status.

Conclusion

Results highlight the role of inequity in predicting brain health and advancing solutions to reduce the cognitive and functional decline in LMICs.
Identification of Persons Living with Dementia Using the Electronic Health Record
Authors: Tan Zaldy S , Qureshi Nabeel , Kremen Sarah , Rhinehart Deana , Gatmaitan Dyane , Spivack Erica , Guinto Augustine , Sicotte Nancy
Published: December 2023

Background

Alzheimer’s disease and related dementias (ADRD) are underdiagnosed in the primary care setting. Proactive screening for cognitive impairment and subsequent evaluation and diagnosis of patients who screen positive are not routinely and reliably performed. As a result, identification of persons living with dementia (PLWD) for enrollment in clinical programs, clinical trials, and research studies can be challenging. The electronic health record (EHR) represents a potentially viable tool to efficiently and accurate identify PLWD.

Methods

In a large academic health care system in the U.S., we performed an EPIC EHR search for PLWD with the intent of enrolling them in an outpatient dementia care management program. The EHR algorithm used the following criteria for dementia: (1) an ICD‐10 dementia diagnosis in the problem list or past medical history or (2) an FDA‐approved drug on their active medication list. We performed chart review for patients who were identified to have potential dementia using this algorithm to confirm dementia diagnosis is documented in clinical notes.

Results

A total of 985 patients were identified by EHR criteria as potentially having dementia. After chart review, 747 (75.8%) were confirmed to have dementia documented in their clinical history and progress notes. One hundred thirty (13.2%) did not have a confirmed dementia diagnosis, 58 (5.9%) had an incomplete dementia evaluation, and 50 (5.0%) had only mild cognitive impairment. In addition, 55 (5.6%) were deceased.

Conclusion

We found that an EHR algorithm can identify patients with dementia in a health plan population. This model may be a useful tool for a focused recruitment of potential participants in clinical trials, research studies, and clinical programs.
The relationship between Event‐Related Potentials and MRI cortical atrophy in a memory disorders clinic
Authors: Morreale Kristina , Marin Anna , Karaca Meltem , Hagan Brenna , Chadalavada Myna , Waskow Emily , DeCaro Renee , Brown Emma , Salat David H , Budson Andrew E , Turk Katherine W
Published: December 2023

Background

There is a need for accessible and affordable ways to assess biomarkers of Alzheimer’s disease (AD). Event‐related potentials (ERPs) are associated with disease severity of AD (Fruehwirt et al., 2019) and are a candidate biomarker for AD (Olichney et al., 2022). There is, however, little understanding of how ERP components relate to neurodegeneration of specific brain structures in AD.

Method

We investigated the correlation between electrophysiology, as measured by ERPs and brain structure using quantitative structural MRI measurements using FreeSurfer. A dataset containing older veteran memory disorders patients (N = 25) from VA Boston Healthcare System was analyzed. Participants completed an MRI and an auditory oddball task ERP paradigm.

Result

An exploratory analysis was performed using a Pearson correlation coefficient to evaluate the relationship between ERPs and the thickness and volume of different cortical areas. There was a negative relationship between P300 target amplitude and inferior temporal volume (p < .05), as well as P300 target latency and thickness of the superior temporal (p < .05) and transverse temporal regions (p < .01). P200 standard amplitude had a positive correlation with thickness in the middle temporal (p < .01), and superior temporal regions (p ≤ .05), and P200 target latency had a negative correlation with thickness of the superior temporal region (p < .05). N200 target amplitude had a negative correlation with the superior parietal volume (right hemisphere = p ≤ .05, left hemisphere = p ≤ .01), left inferior temporal volume (p ≤ .05), and the middle temporal volume (left = p ≤ .05, right = p ≤ .01). N200 target latency was negatively correlated with right superior parietal volume (p ≤ .05).

Conclusion

A correlation was found between ERP measures P200, N200 and P300 with cortical thickness and volume of areas that are commonly impacted by AD pathology, further substantiating use of ERPs as possible AD biomarkers. We conclude that ERPs provide insights as to structural changes of brain structures affected by AD pathology. ERPs could help inform areas of brain atrophy and related patterns of cognitive impairment.
Comparative assessment of α‐synuclein seeding activities in the cerebrospinal fluid of MCI patients phenoconverting to DLB
Authors: Atik Merve , Kondru Naveen Chandra , Savica Rodolfo , Ramanan Vijay K , Graff‐Radford Jonathan , Fields Julie A. , Graff‐Radford Neill R , Day Gregory S. , Ferman Tanis J , Forsberg Leah K. , Boeve Brad F. , Kantarci Kejal , Ross Owen A.
Published: December 2023

Background

Dementia with Lewy bodies (DLB), the second most prevalent form of degenerative dementia, is characterized by pathological α‐synuclein (αSyn) protein aggregation in neurons. Pathological αSyn shows a protein‐seeding phenomenon that may result in aggregation years before clinical symptoms. Studies using Real‐time quaking‐induced conversion (RT‐QuIC) assay show αSyn seeding from peripheral tissue including skin and cerebrospinal Fluid (CSF). Identifying early biomarkers for DLB is essential for accurate diagnosis, and developing effective treatments to slow progression. Herein, we investigate αSyn seeding activities in CSF from patients with mild cognitive impairment with Lewy bodies (MCI‐LB) phenoconverting to DLB.

Method

CSF samples were obtained from 3 MCI‐LB and 2 DLB patients at baseline and two‐year follow‐up appointments. CSF samples were tested for their potential to seed α‐synuclein aggregation using an RT‐QuIC assay. CSF samples were tested by seeding 2 μl of CSF in 98 ul of RT‐QuIC reaction mixture with human recombinant αSyn protein, analyzed on a FLUOstar Omega plate reader. Results were recorded every 30 minutes over a period of 45 hours analyzed based on the reaction kinetics to determine the seeding ability of the α‐synuclein in the CSF samples.

Result

We observed seed amplification at first visit for both DLB patients and one MCI‐LB patient. The absolute quantification of aggregation increased at second visit (2 years apart) for one DLB patient and one MCI‐LB. The other two MCI‐LB patients showed no amplification at baseline visit but showed signal at two‐year visit, by which time all three had phenoconverted to DLB. Interestingly the second DLB patient showed a decline at two‐year follow‐up. The medical and neuroimaging records of that patient indicate that the patient’s cognitive decline began as early‐onset disease (first symptoms at age 50 years).

Conclusion

We demonstrate that measures of seed aggregation in CSF with RT‐QuIC are informative in MCI‐LB and DLB, and may also reflect changes in disease progression and dynamics.
Cataract, cataract surgery, and risk of incident dementia: a prospective cohort study of 300,823 participants
Authors: Ma Lingzhi
Published: December 2023

Background

Considering the increasing rate of cataract surgery and postoperative efficacy, the cataract may be one of the most modifiable risk factors for dementia if surgery reverses the increased risk of dementia caused by cataract.

Method

We used multivariate Cox proportional hazard regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations, with healthy controls as a reference. The same method was used to explore the effects of surgery on the dementia outcomes of cataract patients.

Result

Multivariable Cox proportional hazard models showed that the non‐surgical cataract group had a 21.4% increased risk of ACD (HR: 1.214, 95% CI = 1.012‐1.456, P = 0.037) and a 47.9% increased risk of AD (HR: 1.479, 95% CI = 1.105‐1.981, P = 0.009) in the fully adjusted model. However, there was no difference in dementia risk between the cataract surgery group and the healthy control. Cataract surgery was associated with decreased risk of ACD (HR: 0.632, 95% CI = 0.421‐0.947, P = 0.026) and AD (HR: 0.399, 95% CI = 0.196‐0.812, P = 0.011) compared with non‐surgical group.

Conclusion

Our study supports the hypothesis that cataract surgery reverses the risk of dementia, providing new insights into the prevention and treatment of dementia. Cataract should be considered a significant modifiable risk factor for dementia in dementia prevention strategies.
Perceived Stress and Mindfulness : A Review of Baseline Data for the Practice of Acceptance, Awareness, and Compassion in Caregiving (PAACC) Study
Authors: Sapra Mamta , Hagemann Lauren , Luci Katherine , Savla Jyoti Tina
Published: December 2023

Background

As the prevalence of dementia in Veterans is predicted to increase three‐fold in the coming decades, the Veterans Health Administration has made empowering informal caregivers a top priority. Current evidence‐based caregiver interventions, such as Resources for Enhancing All Caregivers Health (REACH‐VA), focus on cognitive and behavioral strategies to lessen caregiver burden. The Practice of Acceptance, Awareness, and Compassion in Caregiving (PAACC) incorporates mindfulness as the main mechanism for reducing caregiver strain. The goal of this intervention is to help caregivers develop increased present‐focused acceptance and awareness of their reactivity to care‐related stressors rather than focus on aspects of care they cannot change.

Method

The study enrolled 127 dementia caregivers with moderate to severe levels of caregiver burden who were randomized to either cognitive behavior based(REACH‐VA) or mindfulness based(PAACC) support intervention. Study assessed caregivers for stress levels, perceived stress, rumination as well as mindfulness using validated questionnaires.

Results

The mean age of caregivers was 68yrs, with 85% being females and spouses of individuals with dementia. Nearly 75% of the sample have greater than a high school education. Regression analysis of baseline data showed that perceived stress was negatively correlated and associated with mindfulness disposition (b = ‐1.11, p<0.001, R‐square = 0.32). Caregivers benefited from the mindfulness based strategies, and experienced increased acceptance of their caregiver role and greater compassion toward their relative living with dementia.

Conclusion

We project that mindfulness will reduce the impact of the perceived stress and rumination, which is often associated with dementia caregiving and improve quality of life for both individual with dementia and their caregivers.
Impaired Glucose Tolerance and Risk for Mild Cognitive Impairment and Dementia:Results from the SPRINT‐MIND Trial
Authors: Williamson Samuel E , Lovato James F , Gaussoin Sarah A. , Reboussin David M. , Williamson Jeff D.
Published: December 2023

Background

In epidemiological studies, persons with a diagnosis of diabetes mellitus (DM), especially those with coexisting hypertension, have been shown to be at increased risk for dementia.[1‐3] However, the relationship between impaired glucose tolerance (IGT) and future risk of Mild Cognitive Impairment (MCI) and dementia is less clear, especially in persons without diagnosed DM . The SPRINT‐MIND trial (4) provides an opportunity to assess the relationship between baseline glucose level and risk for transition to mild cognitive impairment in the context of hypertension control.

Method

Randomized clinical trial (n = 9,361) conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diagnosed diabetes or history of stroke. Baseline serum glucose obtained fasting and incidence of adjudicated MCI and probable dementia (PD) was calculated. Results were also stratified by age, baseline cardiovascular disease risk, and baseline systolic blood pressure.

Result

At baseline, 4398 participants (58%) had a serum glucose < 100 mg/dl and 3606 (42%) had a serum glucose >100. Overall, 389 (7.9%) of participants in the normoglycemic group and 250 (6.9%) of participants in the impaired glucose tolerance group developed MCI. For incident PD, 204 (4.1%) and 118 (3.3%) cases occurred in in persons with normal vs. impaired glucose tolerance. Incidence MCI or Dementia did not significantly differ when the results were stratified by baseline age or blood pressure.

Conclusion

In persons with hypertension but without diagnosed diabetes, baseline impaired glucose tolerance does not confer elevated risk for MCI or dementia.
Association between Aluminium Levels and Cognitive Decline in Environmentally Exposed Elders
Authors: Gerardo Bianca , Pinto Marina Cabral , Nogueira Joana , Almeida Agostinho , Pinto Edgar , Simões Mário Rodrigues , Freitas Sandra
Published: December 2023

Background

Normal brain functioning depends on metals homeostasis, as imbalances may increase oxidative stress and cause other detrimental intracellular events that lead to cell loss. Furthermore, environmental exposure to toxic metals is hypothesized to induce neuroinflammation and neuropathology, paving the way to neurodegeneration. The aim of this study was to examine whether such Potentially Toxic Elements (PTE) are associated with cognitive performance over time in a sample of elderly individuals of environmentally contaminated regions.

Method

A total of 146 elders permanently residing in environmental risk areas were recruited. Participants completed the Mini Mental State Examination (MMSE) for cognitive assessment and were biomonitored for several PTE through hair and urine analysis. After 5 years, the cognitive assessment was repeated.

Result

Cognitive performance significantly declined from baseline to follow‐up (p < 0.001), with participants scoring on average 4.41 less points on MMSE (Baseline: M = 25.79, SD = 3.520, Md = 27.00; Follow‐up: M = 21.38, SD = 5.343, Md = 21.00). Regression analysis on the relationship between PTE and cognitive performance revealed that Aluminium (β = ‐0.322, p = 0.32) and Zinc (β = ‐0.372, p = 0.15) in hair and Aluminium in urine (β = ‐0.368, p = 0.010) significantly predicted MMSE scores past 5 years of biomonitoring (p = 0.002). Higher contents of these PTE were associated with worse cognitive performance at follow‐up, after controlling the effects of age, education and supplement intake.

Conclusion

Higher levels of Aluminium significantly predict worse general cognitive performance 5 years after biomonitoring across different biological samples. Environmental exposure to this metal may constitute a risk factor for cognitive decline.
Prediction of Dementia Using Machine Learning Methods within a Large Pooled Consortia: The Dementia Risk Prediction Pooling (DRPP) Consortium
Authors: Yu Jingzhi , Stephan John , Krefman Amy , Carolan Padraig , Sedaghat Sanaz , Mansolf Maxwell , Soumare Aicha , Gross Alden L. , Aiello Allison , Singh‐Manoux Archana , Ikram M. Arfan , Helmer Catherine , Tzourio Christophe , Satizabal Claudia L. , Levine Deborah A , Lloyd‐Jones Donald , Briceno Emily M , Sorond Farzaneh , Wolters Frank J. , Himali Jayandra Jung , Launer Lenore J J. , Zhao Lihui , Lopez Oscar L. , Seshadri Sudha , Debette Stéphanie , Judd Suzanne E , Hughes Tim M. , Gudnason Vilmundur , Scholtens Denise , Allen Norrina
Published: December 2023

Background

Machine learning models have been used to create accurate prediction models for dementia. However, many suffer from overfitting and external validation often results in decreased performance. Pooling data from various sources for model training can improve the generalizability of prediction models. We show here a prediction model for dementia developed on pooled data from the Dementia Risk Prediction Pooling (DRPP) Consortium.

Method

Data from 11 longitudinal disease cohorts within the DRPP and relevant risk factors (25 in total) were collected and harmonized at baseline and follow‐up exams. An ensemble tree‐based algorithm, LightGBM, was used to create two prediction models for dementia at or before 10 years. The first model contains all variables in the dataset, and the second clinical model excludes the Mini‐Mental State Examination (MMSE) score and APOE genotype. 5‐fold cross‐validation was repeated 1000 times to tune the model hyperparameters (number of leaves, tree depth, learning rate) to yield the greatest area under the curve (AUC). Feature importance of the model was analyzed via individual feature information gain. Analysis was performed in R 4.1.2.

Results

Among the 55,614 participants from 11 cohorts included in this analysis (Table 1), the first model with all the variables had a cross‐validation AUC of 0.762 (CI: 0.757‐0.767). Counterintuitively, the second model of the without the MMSE and APOE variables yielded an AUC of 0.804 (CI: 0.799‐0.809), which may indicate overfitting in the first model. Feature importance analysis show that age is the most important variable in both models. APOE, MMSE, fasting glucose, and any physical activity are the next most important predictors in the full model (Figure 1). In the second model, fasting glucose, any physical activity, gender, and A1c levels were the next most important predictors (Figure 2).

Conclusion

By pooling various data sources, we can train machine learning models for dementia risk prediction on more diverse data. Further work is needed to compare the performance of these models with models trained on single data sources via external validation. A pooled dataset also offers an opportunity to understand how model performance will change given shifts in the underlying population.
Evaluation of an intergenerational volunteer program for persons living with dementia and their care partners
Authors: Robitaille Annie , Garcia Linda , Qureshi Muhammad , Adams Michaela , Ducharme Francis
Published: December 2023

For people living with dementia, staying connected and engaging in meaningful activities can have a considerable impact on their quality of life. However, people living with dementia are often subject to dementia‐related stigma putting them at increased risk of social isolation. For care partners who might be struggling emotionally and physically, dementia‐related stigma makes it less likely they will seek help when caring for their loved one. The objective of this study was to evaluate the implementation and effectiveness of person‐centered intergenerational volunteer programs for people living with dementia. More specifically, this study evaluated an intergenerational program that pairs people living with dementia in the community and in long‐term care homes with university and high school students to engage in one‐on‐one friendly interactions with the same students for two hours, twice a week (people living with dementia can also choose to be paired with 2 students to receive more visits per week). Results from data compiled between 2021 and 2023 on 165 students, 54 care partners, and 54 people living with dementia collected at baseline, 4 months, 8 months, and 12 months (i.e., ageism, caregiver burden, quality of life) and feedback about the program collected at 4 months, 8 months, and 12 months will be presented. The implementation, adoption, and sustainability of intergenerational programs will also be discussed. Intergenerational volunteer programs have the potential to improve the quality of life of people living with dementia and to promote dementia‐friendly communities and culture change in long‐term care homes.
What is known about intergenerational learning approaches for addressing ageism. including toward individuals with dementia, and attitudes toward aging among future practitioners? Exploring timely scoping review results
Authors: Hand Michelle D , Inoue Megumi D , Kang Hyun D , Tompkins Cathy D , Ihara Emily D , Harvey Kaitlyn D , Parsons Amanda D
Published: December 2023

Background

Intergenerational learning can be used to enhance educational outcomes in higher education, to promote increased wellness in later life, while challenging stereotypes and negative bias toward older adults, including toward individuals with dementia, among future practitioners. Still, research on the mutual benefits and effectiveness of such approaches for addressing ageism among college and university students is limited and continuing to emerge. Accordingly, a scoping review was conducted to explore what is currently known about the use of intergenerational learning approaches in higher education based on available research and how (if at all) such strategies may be relevant for programming focused on improving inclusivity and reducing ageism, including toward individuals with dementia, chiefly among students who will work with older adults during their internships and post‐graduation. This scoping review was also conducted to offer an in‐depth understanding of current implications for practice, education, policy, and research that impacts older adults, including individuals with dementia.

Method

Included were peer‐reviewed and grey sources based on primary qualitative, quantitative, mixed methods research in the English language, which explored intergenerational learning approaches in higher education and attitudes toward older adults and aging. Excluded were sources without clear implications for research, policy, practice or education focused on addressing ageism, including among individuals with dementia.

Results

The search returned 313 potentially relevant articles in Academic Search Complete. Of these, 67 were preliminarily screened in for full text reading after removing duplicates and applying exclusion terms. Upon further review, 37 were initially screened in for thematic analysis, after which another 8 were excluded, owing to thin implications for intergenerational learning strategies in higher education focused on addressing attitudes toward older adults and aging.

Conclusion

Key themes surround intergenerational learning strategies, particularly through service learning and creative expression and attitudes toward older adults, including toward individuals with dementia, perceptions of aging, mutual benefits (e.g., cultural learning and integration), and remaining needs for future research, along with considerations for integration of service learning opportunities into university programs and existing courses. The preliminary results will be discussed, along with implications for research, practice, policy, and education focused on reducing ageism.