bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Later‐Life Education on Trajectories of Cognitive Functionamong U.S. Older Adults
Authors: Wang Nan , Dhingra Radha , Xian Ying , McConnell Eleanor S , Wu Bei , Dupre Matthew E. , Xu Hanzhang
Published: January 2025

Background

Little is known about how education in later life is related to cognitive function in older adults. This study assessed whether participating in later‐life education was associated with better cognitive function over time and whether the benefits differed by sex, race/ethnicity, and prior education level in a nationally‐representative sample of U.S. older adults.

Method

We conducted a retrospective cohort study using six waves of data from the Health and Retirement Study ([HRS] 2008‐2018) that included adults aged ≥ 65 years with no baseline diagnosis of dementia. Cognitive function was measured at baseline and over time using a summary score (range = 0‐35). Later‐life education was measured at every wave and was categorized as attended an educational or training course “at least once a month or more” (10.3%), “not in the last month” (45.5%), or “never” (44.3%). Inverse probability weighting was applied to account for potential selection bias in who participated in later‐life education. The associations between later‐life education and trajectories of cognitive function were estimated using weighted mixed‐effects linear regression models.

Result

Of the 12,099 participants (median [interquartile range] age, 71[67‐77]), engaging in any later‐life education, either at least once a month (0.56 points higher, 95% CI, 0.40 to 0.73; P < .001) or not in the last month (0.55 points higher, 95% CI, 0.45 to 0.65; P < .001) was associated with significantly better cognitive function over time compared to never participating in later‐life education. The association remained constant as people aged and was only partially attenuated after adjusting for sociodemographic, psychosocial, behavioral, and health‐related factors. In addition, the benefits of engaging in any later‐life education on cognitive function were greater in women than in men (at least once a month: 0.30 points higher, 95% CI, ‐0.03 to 0.63, P = .076, not in the last month: 0.24 points higher, 95% CI, 0.04 to 0.43, P = .016) but no significant differences by race/ethnicity or prior educational attainment.

Conclusion

Engaging in later‐life education is beneficial for cognitive function and underscores the importance of continued learning among older adults.
Alzheimer’s disease mortality among Middle Eastern and North African immigrants in the United States
Authors: Kindratt Tiffany B , Amuta Ann O
Published: January 2025

Background

Middle Eastern and North Africa (MENA) adults living in the US experience a higher burden of Alzheimer’s disease (AD) compared to White adults. AD mortality among MENA adults has not been examined. The gap in the literature is because MENA individuals in the US are defined as part of the White race group despite there being differences in health outcomes and lived experiences between MENA and White populations with European origins. Their health also differs from other minoritized immigrant groups, specifically Black African immigrants. The aim of this study is to estimate AD mortality among foreign‐born MENA adults compared to US‐ and foreign‐born White and Black adults.

Methods

Data from publicly available 2000‐2018 National Health Interview Survey and National Death Index Linked Mortality Files through 2019 were analyzed (ages 18+ years). The sample was limited to foreign‐born MENA and US‐ and foreign‐born White and Black adults with a final mortality status captured (n = 763,803). The sample comprised 608,889 US‐born White, 125,803 US‐born Black, 18,751 foreign‐born White from Europe/Russia, 5,172 foreign‐born MENA, and 5,188 foreign‐born Black African adults. All‐cause mortality (%, per 100,000 persons) and AD‐specific underlying cause of death mortality rates (%) were calculated.

Result

All‐cause mortality rate for foreign‐born MENA adults was 5.2%. This was higher than foreign‐born Black (2.3%) but lower than foreign‐born White (13.0%), US‐born Black (12.9%), and US‐born White (13.6%) adults. All‐cause mortality (per 100,000 persons) was highest among US‐born White (13,630) and lowest among foreign‐born MENA (5,240) and Black (2,332) adults. AD was the sixth highest underlying cause of death (4.1%) among MENA immigrants. AD‐specific mortality was similar to foreign‐born White (4.1%) and higher than US‐born White (3.5%) and Black (2.3%) adults.

Conclusion

Findings suggest that foreign‐born MENA adults in the US have a greater burden of AD as an underlying cause of mortality compared to US‐born White and Black adults. In January 2023, the US federal government proposed changes to how race/ethnicity is collected. The new categories include a MENA checkbox to disaggregate this group from White individuals. Our study aligns with the proposed changes to better capture mortality burdens among this minoritized population.
Integrating NACC UDSv3 into non AD/ADRD Cohorts: The Diabetes Prevention Program Outcomes Study in Alzheimer’s Diseases and Related Dementias (DPPOS)‐AD/ADRD Project Experience
Authors: Doherty Lindsay , Luchsinger Jose A. , Temprosa Marinella , Nadkarni Neelesh K. , Goldberg Terry E. , Sherif Hanna , Bowers Anna , Martinez Dianilka , Febres Gerardo J , Sanchez Danurys , Noble James M. ,   Diabetes Prevention Program Research Group
Published: January 2025

Background

The Diabetes Prevention Program (DPP) was a randomized trial for prevention of diabetes in adults with prediabetes (PreD). The DPP Outcomes Study (DPPOS) is the long‐term epidemiological follow‐up of this cohort, studied continuously for over 25 years. DPPOS Phase 4 (DPPOS‐AD/ADRD) began in 2022, with a primary focus on the nature and determinants of cognitive impairment in the surviving cohort.

In coordination with the National Alzheimer’s Coordinating Center (NACC), DPPOS‐AD/ADRD is implementing their Uniform Data Set version 3 (UDSv3), the gold standard used by Alzheimer’s Disease Research Centers (ADRCs), into DPPOS‐AD/ADRD data collection. Additional cognitive exams and screenings administered as part of the DPPOS for the past 14 years are also continuing in DPPOS‐AD/ADRD. As part of the collaboration, DPPOS‐AD/ADRD will send all UDSv3 data to NACC to be compiled with data from other AD/ADRD‐related studies.

We aimed to merge the UDSv3 elements into the existing longitudinal DPPOS data collection schema, while maintaining full fidelity to the UDSv3, and generate reports for streamlined outcomes adjudication.

Methods

Items from the 16 UDSv3 data forms were compared with those from the forms already collected within DPPOS to harmonize similar items, add UDSv3 items not already collected, and ultimately create a dataset uniform with UDSv3. Forms were adapted for electronic data capture (EDC) using the already‐established and validated platform used for DPPOS data collection.

Automated reports were developed, compiling both current and retrospective neuropsychological scores, to facilitate streamlined adjudication of cognitive outcomes.

Results

Items from UDSv3 were either harmonized with or added to existing DPPOS forms or used for DPPOS‐AD/ADRD in their original form from UDSv3.

Reports for cognitive adjudication display both current and retrospective cognitive data (Figure 1). These reports show scoring trends for repeated assessments over time, adjusted scoring percentiles which are color‐coded according to performance, and interpretations of questionnaire and screening assessment scores. Of approximately 3000 total cognitive adjudications expected, 81 have been initiated and are underway.

Conclusions

The DPPOS‐AD/ADRD project has demonstrated that the UDSv3 can be integrated into established, long‐term studies. The DPPOS‐AD/ADRD project can share best practices for other cohorts seeking to add the NACC‐UDSv3 forms.
Design, Characteristics, and Resources from the Diabetes Prevention Program Outcomes Study (DPPOS) AD/ADRD project
Authors: Luchsinger Jose A. ,   Diabetes Prevention Program Research Group
Published: January 2025

Background

Persons with prediabetes and type 2 diabetes (T2D) are known to have higher risk of cognitive impairment (CI), including age‐related cognitive decline, mild cognitive impairment (MCI), and dementia; however, the characteristics of CI and the determinants and mechanisms in prediabetes and T2D remain unclear. Addressing these gaps is critical since over half of the U.S. population aged 60 years and older, who are at risk for AD/ADRD, have prediabetes or T2D.

Methods

The Diabetes Prevention Program (DPP) was a randomized clinical trial among adults with prediabetes which started in 1996 and demonstrated T2D risk reduction with intensive lifestyle or metformin compared with placebo. The DPP Outcomes Study (DPPOS) is a 25‐center observational follow‐up study. Combined, DPP/DPPOS has followed the original cohort for a mean of 23 (range 21‐25) years with extensive longitudinal phenotyping and a comprehensive data and biospecimen repository. To study AD/ADRD in DPPOS we have implemented (a) the NACC UDS version 3 for the adjudication of MCI and dementia; (b) measurement of plasma biomarkers of amyloid, neurodegeneration, and neuroinflammation; (c) examination of plasma measures of brain insulin signaling via neuron‐derived exosomes; and (d) brain MRI and amyloid PET scanning. Figure 1 describes the constructs of the four interrelated projects of DPPOS‐AD/ADRD. Data and biospecimens will be deposited to relevant repositories and available to researchers.

Results

The diverse cohort, originally selected to have prediabetes and at high risk of developing T2D, currently includes 1654 participants, 70% of whom have developed T2D of known duration. Forty‐eight percent are non‐White, and 73% are women. The mean age of the cohort in 1996 was 51 years and now 73 years, with 84% ≥65y. We incorporated the standardized NACC UDS protocol for ascertainment of cognitive status with full fidelity beginning in November 2022, including recorded neurologic exams. Brain imaging began in summer 2023, and exosome extraction began in early 2024.

Conclusions

State of the art procedures, typically used in AD/ADRD research, have been implemented in a large multi‐center non‐AD/ADRD cohort. The proposed measures will supplement those already gathered and provide novel insight into CI in people with prediabetes and T2D.
Development of tau targeted protein degraders for Alzheimer disease
Authors: Wang Lisha , Kumar Rajnish , Pavlov Pavel F. , Winblad Bengt
Published: January 2025

Background

Alzheimer disease (AD) is a progressive neurodegenerative disease that is accountable for the leading case of dementia in elder people. Before, only symptomatic treatments are available for AD. Since 2021, two anti‐amyloid antibodies aducanumab and lecanemab have been approved by the US Food and Drug Administration. However, controversies are still around these two antibodies regarding their efficacy, safety, and substantial economic burden. They also have restricted brain delivery and could not pass through intact neurons to target intracellular proteins. There is still an urgent need for effective, easily administered (oral) and low‐cost drugs for AD.

The intraneuronal accumulation of tau paired helical filaments (PHFs) is one of the hallmarks of AD brain pathology. Lowered efficiency of degradation pathways, such as ubiquitin proteasome system, further exacerbates tau pathologies. Instead of inhibiting protein aggregation, a class of molecules that promote the degradation of targeted protein is known as proteolysis‐targeting chimeras (PROTACs). Since 2016, PROTACs have been applied to resolve tau pathologies, progressing from being based on peptides to fully synthetic small molecules. This exploration is still at the early stage. Here, we aim to develop novel small‐molecule PROTACs as tau targeted protein degraders for AD treatment.

Methods

We performed global molecular docking of tau binders from a public database (bindingdb.org) into the available PHFs 3D structure and selected top ranked compounds. Together with them, ligands binding to E3 ligase, for instance cereblon (CRBN) and carboxyl terminus of Hsp70 interacting protein (CHIP), were used with different linkers to design synthetically accessible PROTACs. The modelling of ternary complex (tau‐PROTACs‐E3 ligase) are performed to rank designed PROTACs and the highly scored will be synthesised. Protein binding affinities and tau‐reducing effects will be evaluated in different cell models: human neuroblastoma SH‐SY5Y cells and mouse embryonic primary neurons.

Results

We perform the development of tau targeted protein degraders according to the methods listed above. We selected the top ranked tau binders and designed new PROTACs.

Conclusions

The most potent PROTACs with least off‐target effects will move on to in vivo study and provide pre‐clinical evidence for novel treatment of AD tauopathies.
Can medical comorbidities modify the clinical evolution of mild cognitive impairment and Alzheimer’s dementia?
Authors: Nguyen Catherine Q N , Ma Liwei , Low Yi Ling Clare , Tan Edwin C.K. , Fowler Christopher J , Masters Colin L. , Jin Liang , Pan Yijun ,   AIBL Research Group
Published: January 2025

Background

Despite the health and societal burden that Alzheimer’s disease (AD) has on the elderly population, the underlying cause is not fully understood. Researchers are investigating possible mechanisms, and current studies have suggested that a number of comorbidities increase/decrease the likelihood of AD onset. The aim of the current study was to explore the associations between various comorbidities and AD in older Australians from an epidemiological perspective.

Method

This study used secondary participant data from the Australian Imaging, Biomarker & Lifestyle (AIBL) study (n = 2436) to perform a quantitative analysis. Univariable logistic regression was used to quantify the relationship between comorbidities and mild cognitive impairment (MCI)/AD, represented as odds ratios (ORs). The top 20 comorbidities were investigated as the exposure and based on the participants’ medical histories. MCI and AD were the outcomes of interest (with cognitive unimpairment as the reference) and were based on participants’ cognitive health diagnoses. Selected comorbidity associations with MCI/AD were also analysed via multivariable logistic regression, by stratifying and adjusting for sex, age, education, smoking, drinking and APOE ε4 allele carrier status.

Result

From the univariable logistic regression, the comorbidities with the strongest odds of developing AD in the AIBL cohort were anxiety, depression, neurological disorders, falls and stroke. Comorbidities with the most reduced odds of developing AD were kidney disease, liver disease and visual defects. These associations remained significant after multivariable logistic regression. When stratified for each covariate, several comorbidity associations observed effect modification from sex and APOE ε4 allele carrier status. When adjusted for all covariates, most of the selected comorbidity associations observed significant confounding. There were moderate similarities between the MCI and AD analyses.

Conclusion

This study presents evidence that certain comorbidities appear to modify the clinical evolution of MCI/AD. Further research is needed to identify the mechanisms behind these associations and the potential modifying effect on MCI/AD.
Early amyloid accumulation and APOE‐ε4 are associated with reduced non‐rapid eye movement slow‐wave activity in cognitively unimpaired adults
Authors: Tort‐Colet Núria , Fernández‐Arcos Ana , Stankeviciute Laura , Minguillon Carolina , Hernández Laura , Knezevic Iva , Sánchez‐Benavides Gonzalo , Suarez‐Calvet Marc , Holst Sebastian C , Garces Pilar , Mueggler Thomas , Zetterberg Henrik , Blennow Kaj , Muñoz‐Lopetegui Amaia , Arqueros Aurora , Iranzo Álex , Gispert Juan Domingo , Molinuevo Jose Luis , Grau‐Rivera Oriol
Published: January 2025

Background

Poor sleep is associated with cognitive decline, and ∼45% of Alzheimer’s disease (AD) patients experience sleep disturbances. Emerging evidence suggests that reduced non‐rapid eye movement (NREM) slow wave sleep (SWS) is linked to amyloid accumulation and APOE ε4‐related genetic vulnerability to AD. Here, we investigate the effects of amyloid and APOE status on SWS, and their interaction, in a cohort of cognitively unimpaired (CU) individuals at higher risk of AD.

Method

We analyzed data from 80 sleep medication free participants (65.26 years old on average, 55% females, Table 1) from the AlfaSleep project, which involves characterization with polysomnography, APOE genotyping, CSF amyloid‐β (Aβ) 40 and Aβ42 (Roche NeuroToolKit), and [18F]flutemetamol‐PET, among other measures. Participants were classified as amyloid positive (A+) using either CSF Aβ 42/40 ratio (<0.071, N = 75), or amyloid PET (>12 Centiloids, N = 5) thresholds for early amyloid deposition.

We computed average power spectral densities (PSD) from NREM sleep 30‐s epochs in frontal electroencephalogram channels, and power of slow oscillations (SO), delta and slow wave activity (SWA) as the area under the PSD curve between 0.5‐1Hz, 1‐4Hz and 0.5‐4Hz, respectively. We log‐transformed SWS metrics due to non‐normal distribution. We used linear regression models to test the main effect of amyloid or APOE status on SWS metrics in separated models, and next we entered both in the same model. Finally, we the tested interaction between APOE and amyloid status on SWS metrics. Models were adjusted by age, sex, and apnea‐hypopnea index (AHI).

Result

Both A+ status and APOE‐ε4 carriership were associated with significantly lower power in SO and SWA in separated models (Figure 1A). When combining both in the same model, only the effect of APOE on SO power remained significant, as well as a trend for lower SWA (Figure 1B). Interaction analyses yielded no significance.

Conclusion

Early amyloid accumulation and APOE‐ε4 carriership are associated with SWS disruption in CU adults, with APOE‐ε4 carriers probably being particularly vulnerable to SWS disruption. Longitudinal studies spanning younger age individuals are needed to characterize the contribution of APOE‐ε4 to SWS disruption and to test whether preventive interventions targeting SWS could help to reduce AD dementia risk.
Validating the CogSleep Screener in older adults at a memory and cognition clinic
Authors: Kong Shawn Dexiao , Schrire Zoe M , Lin Pinghsiu , Simonetti Simone , Cross Nathan , Mowszowski Loren , Naismith Sharon L , Clinic Healthy Brain Ageing Research
Published: January 2025

Background

While sleep disturbances are prevalent in older people and are linked with poor health and cognitive outcomes, screening for the range of sleep disturbances is inefficient and therefore not ideal nor routine in memory and cognition clinic settings. We aimed to develop and validate a new brief self‐report questionnaire for easy use within memory and cognition clinics.

Method

Older adults (N = 402, mean age 67.3 years, range 50‐86, 63.6% female) were recruited from a memory and cognition research clinic. All participants completed a comprehensive medical, neuropsychological and mental health assessment, alongside self‐report instruments, including existing sleep questionnaires and a new 10‐item sleep questionnaire, the CogSleep Screener. We examined the factor structure, convergent validity, internal consistency, and discriminant validity of this novel questionnaire.

Result

Using exploratory principal component analysis, a 3‐factor solution was generated highlighting the factors of Insomnia, Rapid Eye Movement (REM) Symptoms and Daytime Sleepiness. Each factor was significantly correlated with currently used sleep questionnaires for each subdomain (all Spearman rho>0.3, all p<.001), suggesting good convergent validity. Internal consistency was also good (Crobach’s α = .73). Receiver operating characteristic curves showed good discriminative ability between participants with and without sleep disturbances (all area under curve>0.7, all p<.01).

Conclusion

The CogSleep Screener has good psychometric properties in older to elderly adults attending a memory and cognition clinic. The instrument has the potential to be used in memory clinics and other clinical settings to provide quick and accurate screening of sleep disturbances.
Personality as a Factor Underlying Cognitive Reserve
Authors: Coors Annabell , Lee Seonjoo , Habeck Christian G , Stern Yaakov
Published: January 2025

Background

Cognitive reserve is a concept that explains why cognitive performance can be better than would be expected given the level of brain pathology. In this project, we investigated whether certain personality traits are a factor underlying cognitive reserve. If so, individuals with these personality traits would show better cognition and less cognitive decline than would be expected given their level of age‐related brain changes.

Method

The cross‐sectional analyses were based on 399 healthy adults aged 19‐80 and the longitudinal analyses were based on 273 individuals. The mean follow‐up time was 5 years (SD = 0.7 years). The International Personality Item Pool questionnaire was used to assess the BIG5 personality traits openness, conscientiousness, extraversion, agreeableness, and neuroticism. Each cognitive domain (perceptual speed, memory, fluid reasoning, and vocabulary) was measured with up to 6 tasks. Cognitive domain‐specific brain status variables, derived from 77 structural brain measures using elastic net regularization, explained up to 43.1% of variance in cognitive performance.

Result

Higher openness was associated with higher fluid reasoning and better vocabulary after adjusting for the cognitive domain‐specific brain status variables, age, and sex. Additionally, lower brain status was only associated with increased decline in perceptual speed among individuals with low openness. In contrast, in individuals with high openness, brain status was almost unrelated to change in perceptual speed.

Conclusion

High openness increases cognitive reserve and should be promoted across the lifespan.
Racial differences in blood pressure variability in the SPRINT trial
Authors: Sible Isabel , Nation Daniel A.
Published: January 2025

Background

Blood pressure (BP) management is an accessible therapeutic target for dementia prevention. BP variability (BPV) is a newer aspect of BP control recently associated with cognitive decline, dementia and Alzheimer’s disease (AD), independent of traditionally targeted mean BP levels. Most of this work has relied on largely non‐Hispanic White study samples in observational cohorts. It remains unclear what role BPV may play in dementia‐related racial/ethnic health disparities. We examined whether BPV differed by race in the SPRINT BP clinical trial.

Method

In this post hoc analysis of the SPRINT trial, 8034 participants (median (SD) 67 (9.3) years; 34.8% female; 28.6% Black; 58.9% White; 10.8% Hispanic; 1.7% Other) underwent 4 BP measurements over a 9‐month period after treatment randomization (standard [<140 mmHg systolic target] vs intensive [<120 mmHg systolic target] BP lowering). Visit‐to‐visit systolic BPV was calculated as variability independent of mean. Racial groups (Black vs White vs Hispanic vs Other) were compared on BPV using ANCOVA models adjusted for age, sex, mean BP over the same 9‐month period, and number of antihypertensive medications used. Analyses were stratified by standard vs intensive treatment group.

Result

Under standard BP lowering treatment, systolic BPV significantly differed by race (F
3,3969 = 10.11, p < .001). When compared to Hispanic participants (mean (SD) 8.96 (1.1) mmHg), systolic BPV was higher in Black (9.26 (1.0) mmHg; .30 mmHg difference; p < .001), White (9.20 (1.0) mmHg; .24 mmHg difference; p < .001), and Other (9.31 (.9) mmHg; .35 mmHg difference; p = .01) participants. Racial groups did not significantly differ on systolic BPV under intensive BP treatment (F
3,3978 = 1.41, p = .24).

Conclusion

Although the SPRINT trial found no racial differences in treatment effects on cardiovascular benefits/risks, our findings suggest BPV differs by race, particularly under standard BP treatment. BPV is an emerging risk factor for dementia that may require unique treatment approaches beyond traditional lowering strategies. Findings could have therapeutic implications for patient‐centered care strategies aimed at reducing dementia risk and enhance our broader understanding of health disparities in vascular health relevant to AD risk.
Accelerating randomized clinical trials in Alzheimer’s Disease using generative machine learning model forecasts of progression
Authors: Yakubu Amin , Bogert Jennifer , Zhuang Run , Wittenberg Gayle , Pozniak Christine , Zhang Yi , Kusiak Coco , Turner Michelle , Hansen Bryan , Walsh Jonathan R.
Published: January 2025

Background

Pivotal Alzheimer’s Disease (AD) trials typically require thousands of participants, resulting in long enrollment timelines and substantial costs. We leverage deep learning predictive models to create prognostic scores (forecasted control outcome) of trial participants and in combination with a linear statistical model to increase statistical power in randomized clinical trials (RCT). This is a straightforward extension of the traditional RCT analysis, allowing for ease of use in any clinical program. We demonstrate the application of these methods retrospectively on 3 pivotal Phase III clinical trials in mild‐to‐moderate AD (NCT00236431, NCT00574132, and NCT00575055).

Method

A probabilistic deep learning model was trained on the trajectories of nearly 7000 participants who had varying degrees of cognitive impairment, ranging from mild cognitive impairment (MCI) to moderate AD. These trajectories were collected observational studies and the control arms of RCTs. This trained model was used to forecast the control outcomes of participants in the three trials retrospectively, by entering their individual trial baseline data. The resultant forecasts are known as prognostic scores and represent comprehensive predictions across a broad range of AD outcomes.

We evaluated the potential reduction in estimated variance and how this could translate to required sample size by incorporating the prognostic score as a covariate in the primary linear statistical model of each study, analyzing the 11‐component Alzheimer’s Disease Assessment Scale‐Cognitive Subscale (ADAS‐Cog11) and the Clinical Dementia Rating Sum‐of‐Boxes (CDR‐SB) endpoints as applicable.

Result

Prognostic scores have the potential to decrease estimated variance between 5% to 10% and placebo arm sample size between 7% and 17% in the 3 studies when comparing standard + prognostic score vs. standard adjustment.

Conclusion

Prognostic scores have the potential to increase the statistical power in clinical trials; this would enable a reduced number of subjects required to detect a significant treatment effect. Potential sample size reduction during trial planning must be carefully estimated using independent validation studies to reduce the risk of under‐powering the trial.
Exploring Agency in Dementia: Care Staff Perspectives and Recommendations
Authors: Immonen Annikka
Published: January 2025

Background

My dissertation focused on the cultural and historical images of agency in person with dementia. In this partial study I examined care staff, who were also in a caregiver role, and their perceptions of how neurocognitive disorders (NCDs) change agency of a person. This role enabled for them to observe the entire disease process.

Methods

The research utilized data from a survey of care staff (n = 191) and Finnish dementia care textbooks spanning 1985 to 2019 (77 books). The theoretical framework consisted of communicative (Holzkamp), dynamic (Thomas and Znaniecki, Jyrkämä), and embodied (Kontos) agency of a person with dementia.

Results

Before the onset of illness, care staff depicted their loved ones as social, cheerful, and purposefully active individuals with various possibilities for activities and skills to lead unique lives. The narratives of agency emphasized purposeful and intentional activity, as well as physical engagement.

As neurocognitive disorders progressed, care staff observed a decline in agency, particularly linked to cognitive impairment. The narratives highlighted loss of abilities, memory, and social agency. Embodied agency was underemphasized in the narratives. The non‐verbal body language of persons with dementia was weakly presented. Agency was interpreted through the lens of spoken language and cognitive functioning.

Conclusion

In both textbooks and accounts from care staff, the non‐verbal body language of people with dementia was inadequately portrayed.

To optimally fulfil the agency of people with dementia, the study recommends actively observing their embodied agency and assessing their needs based on these observations. In response to the research findings, a remote learning course is currently under development to assist care staff in recognizing and supporting embodied agency of people with dementia.
Cognitive impairment and dementia in a nationally representative sample of older adults receiving care for incident TBI
Authors: Kornblith Erica S , Diaz‐Ramirez L. Grisell , Yaffe Kristine , Boscardin W John , Gardner Raquel C.
Published: January 2025

Background

Cognitive problems are thought to increase vulnerability to geriatric traumatic brain injury (TBI) due to increased fall risk, but little is known about prevalence of cognitive impairment and Alzheimer’s disease and related dementias (ADRD) among elders who receive treatment for a TBI.

Method

Enrollees 65 and older in the nationally representative Health and Retirement Study (HRS) who consented to link survey data to Medicare claims and without a TBI prior to enrollment were studied. We used claims 2000‐2018 to obtain incident TBI diagnoses, defined using inpatient and outpatient International Classification of Disease (ICD) 9 and 10 codes received the same day as an emergency room (ER) visit code and a computed tomography (CT) scan code. Sociodemographic and health factors were defined at baseline interview. Baseline cognition was defined using Langa‐Weir Dementia Probability, a predictive model that classifies each respondent as ADRD; cognitive impairment, no dementia (CIND); or normal cognition.

Result

Of respondents who experienced incident TBI (n = 797), 74% were classified as normal cognition, 19% as CIND and 7.1% ADRD at baseline. In the no‐TBI group (n = 8442), 68% had normal cognition, 23% CIND, and 10% ADRD (p<0.01). In sensitivity analyses considering TBI ± ER treatment and/or CT, results were similar. However, in multivariate models examining association of incident TBI with baseline sociodemographic, medical, and cognitive characteristics, neither CIND nor ADRD were associated with TBI status (p’s = 0.30 and 0.51, respectively). Instead, Black race (p<0.01), male sex (p = 0.02), higher education (p = 0,01), lung disease (p<0.01), higher neighborhood socioeconomic status (SES, p<0.01), and older age (p<0.01) were associated with membership in the no‐TBI group.

Conclusion

Our results suggest prevalence of baseline cognitive impairment and dementia is lower among elders treated for an incident TBI during study follow‐up, compared to the no‐TBI group. CIND/ADRD may protect against TBI through reduced activity or increased support with daily tasks. Alternatively, elders with CIND/ADRD may have reduced health care access or utilization. Moreover, demographic and contextual factors like age, gender, education, and neighborhood SES appear to be more meaningful predictors of incident TBI in this sample, vs. baseline cognition.
Mild pharmacological inhibition of mitochondrial complex I restores synaptic density in hippocampus of APP/PS1 mice assessed by 3D EM reconstruction
Authors: Keller Noah , Christensen Trace , Trushina Eugenia
Published: January 2025

Background

Alzheimer’s disease (AD) is an age‐dependent neurodegenerative disorder with limited treatment options. As it progresses, synapse degeneration is the most important feature contributing to cognitive dysfunction. Mitochondria supply synapses with ATP for neurotransmitter release and vesicle recycling and buffer calcium concentrations. In AD, mitochondrial function is disrupted leading to energetic stress and synapse degeneration. We have identified a novel therapeutic strategy that blocks neurodegeneration and protects cognitive function in multiple mouse models of AD (amyloid and tau pathologies) via mild pharmacological inhibition of mitochondria complex I, which results in the activation of adaptive stress response and subsequent improvement of mitochondrial function.

Method

Analysis of mitochondrial morphology and synaptic density was done in the hippocampal CA1 tissue from APP/PS1 and non‐transgenic (NTG) mice treated with vehicle or mild complex I inhibitor CP2 for 14 months starting after the development of cognitive dysfunction and neurodegeneration. A serial block‐face scanning electron microscopy (SBF‐SEM) and three‐dimensional (3D) EM reconstructions were employed to determine the synaptic density and mitochondrial morphology and distribution associated with different dendritic spine types.

Result

We demonstrate that APP/PS1 mice have significantly reduced synaptic density in the hippocampus compared to the NTG littermates. CP2 treatment restores synaptic density to the levels observed in NTG mice evident by the increase in the number of synaptic densities visible in the electron micrographs. Mitochondrial morphology and association with synapses are currently being investigated.

Conclusion

Our data are consistent with previously conducted electrophysiology recording in acute brain slices from APP/PS1 and NTG mice treated with vehicle or CP2, demonstrating restoration of long‐term potentiation (LTP) after chronic CP2 treatment. Additionally, it suggests that 3D EM‐based assessment of synaptic density could serve as a surrogate marker for LTP and cognitive function useful for drug discovery.
Measuring preferences for meaningful activity in assisted living residents with dementia
Authors: Levy Sorah
Published: January 2025

Residents with dementia living in assisted living settings report that participating in activities contributes to their psychosocial well‐being and evidence suggests it has the potential to address outcomes such as improved mood, reduced agitation, and increased feelings of social connection. However, assisted living residents with dementia are infrequently asked about their preferences and interests for activities and those preferences might change over time along with their cognitive or physical abilities. Further it can be challenging for staff to focus on engaging residents in meaningful activity when they have competing demands to perform other care responsibilities. There is a need for practical tools to help assisted living staff evaluate preferences and identify opportunities for meaningful activity for residents with dementia that are tailored to those preferences. The purpose of this study was to develop a measurement tool to evaluate preferences and establish goals for meaningful activity, the Assessment of Resident Preferences for Meaningful Activity Tool. This tool was developed specifically for assisted living residents with dementia and collects brief information about the resident’s background (e.g. where they grew up, what they did for work, hobbies etc.) and includes a list of short answer prompts about what is meaningful to the resident (e.g. “I feel good about myself when…”, “I feel accomplished when…”, “I feel a sense of joy when…”). The information collected in this tool is used to develop an individualized plan for engaging the resident in meaningful activity. The tool was completed with assisted living residents with moderate to severe dementia enrolled in the randomized controlled trial, Meaningful Activities for Managing Behavioral Symptoms of Distress (MAC‐4‐BSD). A description of the tool will be presented along with key strategies to facilitate the implementation of this tool in practice for engaging residents with dementia in meaningful activity.
Examining the associations between pain, function, and behavioral symptoms with engagement in meaningful activity among residents with dementia in assisted living
Authors: Holmes Sarah D
Published: January 2025

Background

Engagement in meaningful activity is beneficial for residents with dementia and is associated with improved quality of life. Meaningful activity refers to activities that provide meaning and value to the person and are tailored to individualized interests and preferences. The purpose of this study was to examine factors associated with engagement in meaningful activity among residents with dementia in assisted living. Specifically, it was hypothesized that function, pain, and behavioral symptoms would be associated with engagement in meaningful activity after controlling for residents’ age, gender, comorbidities, and cognition.

Method

This study included baseline data collected from the randomized controlled trial, Meaningful Activities for Managing Behavioral Symptoms of Distress (MAC‐4‐BSD). Assisted living residents were eligible if they were ≥55 years old, live in a participating setting, and screen positive for dementia based on the Saint Louis University Mental Status exam (SLUMS) and AD8 Dementia Screening Interview. Residents were excluded if they were enrolled in hospice, admitted for short term respite, or had a significant neurological condition not related to ADRD. Residents’ engagement in meaningful activity was evaluated based on the Engagement in Meaningful Activities Survey (EMAS). Stepwise linear regression was used to examine resident factors associated with engagement in meaningful activity.

Result

A total of 71 residents from 5 assisted living settings were included in the sample. Most participants were female (n = 52, 73%), White (n = 62, 87%), and mean age was 85 years old (SD = 8.2). Controlling for age, gender, comorbidities, and cognition, pain was significantly associated with engagement in meaningful activity (b = ‐2.1, p = .03). There were no associations between function and behavioral symptoms with engagement in meaningful activity (p>.05) and the model explained 6.1% of the variance in engagement in meaningful activity.

Conclusion

Findings from this study offer insights into residents’ engagement in meaningful activity in assisted living. Ongoing research is needed to consider the impact of the physical and social environment and other possible factors that may also be associated with meaningful activity.
The role of moderate‐vigorous physical activity and sedentary behavior on cognitive function: Cross‐sectional analysis in U.S. POINTER
Authors: Halloway Shannon , Leng Xiaoyan , Desai Pankaja , Stone Katie L , Baker Laura D
Published: January 2025

Background

Healthy lifestyle behaviors can help prevent or delay cognitive impairment in older adults, including increasing moderate‐vigorous physical activity (MVPA). However, across studies examining effects of MVPA on cognitive function, findings are mixed. This may be partially explained by higher levels of sedentary behavior (SB) that may offset some benefit of MVPA. We aim to examine associations of MVPA and SB with cognitive function (global cognition, and the memory, executive function, and processing speed domains) and explore the degree to which SB offsets benefits of MVPA on cognitive function in older adults.

Method

Cross‐sectional analyses were conducted using baseline data from 1680 participants from the U.S. POINTER trial, a lifestyle trial to prevent cognitive decline in at‐risk older adults without cognitive impairment at baseline. Cognitive function (global cognition and three domains) was comprised of composites of memory, executive function, and processing speed derived from pre‐specified scores of the test battery. MVPA and SB were assessed using validated self‐report questionnaires. Multiple linear regression was conducted to examine separate and combined effects of MVPA and SB on cognitive function. Additional models were conducted to examine the MVPA*SB interaction. Covariates included age, sex, racial and ethnic background, and education.

Result

On average, participants were 68.4 years of age, 66.3% were of White racial background, 29.6% reported education less than college, and reported engaging in 4.3 hours/week of MVPA and 70.0 hours/week of SB. In the unadjusted models examining the separate effects of MVPA and SB with cognitive function, higher MVPA was related to better processing speed (b = .03, p = .005), while lower SB was related to better global cognition (b = ‐.002, p = .003), episodic memory (b = ‐.002, p = .026, executive function (b = ‐.002, p<.001), and processing speed (b = ‐.002, p<.001). These findings did not remain significant once adjusted for sociodemographics. The combined effects of MVPA and SB or the MVPA*SB interaction were not statistically significant.

Conclusion

Although MVPA and SB were found to be each separately related to better cognitive function in older adults, associations did not remain once considering the influence of sociodemographics. In our upcoming analyses, we will examine associations using objective measures of MVPA and SB.
Fostering Equity in Dementia Care: The Vital Role of Culturally Sensitive Technology
Authors: Khan Arshia A , Imtiaz Rana Z
Published: January 2025

This perspective abstract highlights the critical demand for culturally sensitive technology in dementia caregiving due to the heightened risk and unique challenges faced by individuals from diverse backgrounds. The escalating prevalence of dementia necessitates a caregiving paradigm shift, especially in the context of diverse cultural backgrounds. Research consistently underscores the existence of cultural disparities in dementia risk, diagnosis, and care outcomes, emphasizing the urgent need for culturally sensitive technology in dementia care.

Individuals from diverse cultural backgrounds often face unique challenges in accessing and receiving adequate dementia care. These challenges may stem from variations in communication styles, beliefs, and societal attitudes toward dementia. Culturally sensitive technology has the potential to bridge these gaps by tailoring interventions to align with specific cultural contexts. It can enhance communication, understanding, and overall caregiving effectiveness, providing personalized support that respects the cultural nuances of those affected by dementia.

Moreover, incorporating cultural sensitivity into technology design not only addresses disparities but also contributes to more inclusive healthcare practices. Culturally tailored technologies can empower caregivers with tools that recognize and respect diverse perspectives, fostering a more collaborative and patient‐centered approach. In essence, the need for culturally sensitive technology in dementia care is paramount to ensuring equitable access, improving outcomes, and promoting a holistic understanding of the multifaceted challenges faced by individuals from diverse cultural backgrounds affected by dementia. This imperative aligns with the broader goal of enhancing the quality of life for all individuals affected by dementia while fostering a more inclusive and compassionate healthcare environment.
BreatheBot Buddy: Fostering Cognitive Well‐being with a Cuddly Companion for Regulated Breathing
Authors: Khan Arshia A , Sawchuk Matthew , Saheel Sabir , Quigley Jack , Heck Detlef
Published: January 2025

Background

Regulated breathing is increasingly recognized as a vital component in enhancing cognition. Scientific studies suggest that intentional and controlled breathing techniques, such as deep and rhythmic breathing, can promote relaxation, reduce stress, and improve oxygen flow to the brain [1, 2]. Consequently, this may contribute to heightened cognitive function, better concentration, and increased mental clarity, accentuating the importance of incorporating mindful breathing practices as a potential avenue for cognitive improvement [3].

The increasing recognition of the cognitive benefits of regulated breathing is leading to the development of innovative technologies, such as robots, for better breathing practices. These technologies can be used to potentially enhance the cognitive well‐being and mindfulness of people in their daily routines.

Methods

In order to accomplish a breathing robot, the entire design consists of two linear actuators controlled by an L298N Motor Driver Interface and a Raspberry Pi 3B. The Raspberry Pi coordinates both linear actuators to extend, hold, and contract in opposite directions for 4 seconds at each stage. Additionally, the mechanical design utilizes two “push caps” that push at the sides of a contained space, such as a stuffed animal, simulating breathing (see Fig. 1). This design simulates a breathing pattern in any stuffed animal (see Fig. 2).

Results

The developed robot underwent rigorous testing in both a lab and poster presentation setting. Various case studies were examined during the poster presentation, revealing the effectiveness of a tool designed to aid in regulated breathing. The present robot demonstrated increased participant engagement in mindful breathing practices, which suggests a promising avenue for leveraging robot‐assisted therapies to enhance cognitive well‐being in people.

Conclusion

The present project aimed to build a robot that fosters cognitive well‐being through regulated breathing. The case study findings of this project highlight the effectiveness of a cuddly bear‐shaped robot as a valuable tool for promoting regulated breathing, offering positive implications for integrating such robotic assistance in enhancing cognitive well‐being.
Translating high throughput screens in C elegans and microglia to humans with Medicare data to repurpose drugs to treat Alzheimer’s disease
Authors: Litke Rachel R , Arora Arushi , Wang Yihan , Aldridge Melissa D , Ko Fred C , Sandin Sven , Sano Mary , Reichenberg Abraham , Mobbs Charles V
Published: January 2025

Background

Despite increasing knowledge of the etiology of neurodegenerative diseases, translation of these benefits into therapeutic advances for Alzheimer’s Disease and related diseases (ADRD) has been slow. Drug repurposing is a promising strategy for identifying new uses for approved drugs beyond their initial indications. We developed a high‐throughput drug screening platform aimed at identifying drugs capable of reducing proteotoxicity in vivo (Aß toxicity in Caenorhabditis elegans) AND inhibiting microglial inflammation (TNF‐alpha IL‐6), both implicated in driving AD(figure attached with sample of results in C. elegans). These screens led us to prioritize 50 potentially protective FDA‐approved drugs. We propose to test our screening results in humans using administrative claims data collected from the Centers for Medicare and Medicaid Services

Method

This is an observational retrospective pharmaco‐epidemiological longitudinal cohort study. The cohort is a random sample of 1,000,000 beneficiaries, aged 65‐75 years, followed for 10 consecutive years, requested from CMS. Files include MedPar, Outpatient, Carrier, Hospice to maximize inclusion of AD beneficiaries according to Bynum algorithm, and Part D event for drug prescription details. We will use Cox regression, to compute Hazard Ratios and associated 95% confidence intervals, of the association between drug exposure status and the risk of ADRD. We will examine potential confounding by indication, drug target, and competing risks.

Result

1/We propose to assess if drugs which reduce Ab toxicity in a C. elegans model of AD AND reduce microglial inflammation reduce the risk of developing ADRD in humans, using Medicare claims. 2/We propose to assess if drugs which reduce inflammation, reduce the risk of developing ADRD in humans, using the Medicare claims.

Conclusion

The end goal of the study is to identify drugs to be repurposed to treat ADRD and to accumulate strong epidemiological evidence in addition to the existing evidence from the model organism C. elegans and cell culture studies.