bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating segregated school attendance as a mediator of geographic inequities in late‐life cognitive function: evidence from the Study of Healthy Aging in African Americans (STAR)
Authors: Gutierrez Sirena , Whitmer Rachel A. , Lor Yi , George Kristen M. , Barnes Lisa L. , Mayeda Elizabeth Rose , Allen Isabel Elaine , Glymour M. Maria , Torres Jacqueline M , Gilsanz Paola
Published: January 2025

Background

Being born in the Southern US is associated with poorer cognitive health and related cardiovascular outcomes in late life, especially among Black Americans. Geographic disparities in brain aging may be mediated by school segregation; school segregation has been disproportionately high in the South given historical and contemporary policies and practices.

Method

This study included 727 Black adults ages 50+ (mean 68.8 (8.8±SD) years) living in Northern California from the Study of Healthy Aging in African Americans (2018). We employed linear regression models to estimate associations between Southern US birth and domain‐specific cognitive function z‐scores, adjusting for early‐life covariates. Utilizing mediation analysis, we decomposed the total effect of Southern birth into natural direct effects and natural indirect effects via self‐reported ever attending a segregated school at grade 1, 6, 9, or 12.

Result

The 38% of participants born in the South averaged older age (74.9 vs. 65.0 years), had less educated parents (38.4% vs. 15.4% with less than high school), and were more likely to have attended segregated schools (71.7% vs. 18.1%) compared to those born in other regions. Southern birth was associated with lower late‐life executive function (β[95% CI] = ‐0.18 [‐0.33, ‐0.03]) and semantic memory (‐0.36 [‐0.52, ‐0.20]); estimates were imprecise for verbal episodic memory (‐0.07 [‐0.23, 0.09]). Under the assumptions for mediation analyses, the estimated direct effect of Southern birth, not mediated by attending a segregated school, was ‐0.12 [‐0.29, 0.05] for executive function, ‐0.19 [‐0.39, 0.00] for semantic memory, ‐0.11 [‐0.27, 0.05] for verbal episodic memory. Attending a segregated school mediated 38% and 47% of the total effect of Southern birth on executive function (indirect effect: ‐0.07 [‐0.17, 0.03]) and semantic memory function (indirect effect: ‐0.17 [‐0.28, ‐0.06]).

Conclusion

School segregation may be an important mechanism underlying geographic inequities in late‐life health in the US. Interventions to reduce persistent de facto school segregation may help ameliorate these inequities. Future research should consider other mechanisms related to the schooling environment (e.g. resources, quality) that may be additional targets of intervention.
Longitudinal multicenter head‐to‐head harmonization of tau‐PET tracers: an overview of the HEAD study cohort
Authors: Lussier Firoza Z , Povala Guilherme , Bauer‐Negrini Guilherme , Amaral Livia , Cehula Juli , Fine Devin J , Lemaire Peter , Bloomquist Madeleine , Pascual Belen , Gordon Brian A. , Lowe Val J. , Oh Hwamee , soleimani‐meigooni David N. , Rosa‐Neto Pedro , Tudorascu Dana , Jagust William J. , Klunk William E , Baker Suzanne L. , Pascoal Tharick Ali
Published: January 2025

Background

Standardizing tau pathology quantification in vivo is challenged by differences in binding characteristics between tau‐PET tracers. The HEAD study aims to generate a leading, longitudinal head‐to‐head dataset of MK‐6240, Flortaucipir, RO948, and PI‐2620 tau‐PET to harmonize these tracers' outcomes and develop tools allowing for the generalization of findings across large studies and trials. Here, we present current advancements in building the HEAD study cohort and dataset.

Methods

The HEAD study is managed at the University of Pittsburgh. HEAD comprises several sites across the US and Canada in which 620 subjects (young, cognitively unimpaired, mild cognitive impairment, and Alzheimer’s disease (AD)) will undergo tau‐PET with at least two tracers, amyloid‐PET with PiB or NAV4694, MRI, blood collection, and standardized neuropsychological testing at baseline and at 18‐month follow‐up. PET and MRI acquisition parameters are based on ADNI4 protocols and neuropsychological testing employs the NACC Uniform Data Set. The National Centralized Repository for AD serves as the biorepository for blood samples and the Laboratory of Neuroimaging provides a centralized database for imaging and neuropsychological archiving. PET data is reconstructed to maximize cross‐scanner harmonization and is processed uniformly similarly to ADNI4 PET.

Results

In one year of active enrollment (Jan 2023‐Jan 2024), 362 participants were enrolled at six active sites; over 80% of participants completed neuropsychological testing and MRI, and over 70% completed Flortaucipir, MK‐6240, and amyloid‐PET, with a mean tau‐PET acquisition window of 29.1 days. RO948 and PI‐2620 tau‐PET are additionally acquired in a subset currently including 41 participants (Figure 1). Current HEAD cohort demographics including age, sex, underrepresented populations, and group distributions, APOEε4 carrier status, and amyloid positivity are shown in Figure 2. A case of a subject with AD with all 4 tau‐PET tracers acquired head‐to‐head within 49 days is shown in Figure 3.

Conclusion

The HEAD study represents a continued effort in the optimization of AD imaging biomarkers. Baseline data collection is projected to be completed in 2024; results being generated by multiple groups from this dataset will provide novel and crucial guidance on the use of tau‐PET tracers in research, clinical trials, and prospectively in clinical practice.
Cross‐sectional study of the impact of psychosocial factors on cognitive and behavioral symptoms in patients at the University Hospital of Buenos Aires
Authors: Dunovits Cynthia , Brusco Luis Ignacio , Olivar Natividad , Germani Sandra
Published: January 2025

Background

Increasing evidence points to the possible risk roles of psychosocial factors (lack of education, active social participation, physical exercise and mentally stimulating activity, economic instability, traumatic life events) in the pathogenic process and clinical manifestation of dementia disorders.

In recent years in our country, in the context of a complex inflationary process, there has been an increase in all indicators of vulnerability and poverty, exceeding 40% of the population below the poverty line in 2023 and around 9% below the indigence line.

Method

In the context of International Alzheimer’s Day, the Alzheimer’s Disease Awareness Week was held at the Hospital de Clínicas of Buenos Aires. In it, spontaneous attention was provided to 100 patients between 60 and 85 years old with cognitive complaints, evaluating education, occupation, socio‐environmental variables along with anxiety scales (GAD); affective (PHQ), minimental and NPI.

Result

In our sample of one hundred patients, a clear prevalence of women in the consultation with a medium educational level was observed. An increase in the incidence of anxious symptoms (40%) and depressive symptoms (40%) was evident; followed by irritability (30%); sleep disturbances (35%); apathy (20%).

Conclusion

Psychosocial factors play a fundamental role in the incidence, onset and progression of cognitive conditions, which is why they should be a priority in dementia prevention policies. The prevalence of women’s consultations and their earlier access in a preventive modality also shows their more fluid contact and circulation in the health system and particularly in primary care.
Amyloid Plaque Reduction as a Surrogate Marker of Efficacy: Assessment of Amyloid PET and Change in CDR‐SB Utilizing Semi‐Mechanistic Model
Authors: Willis Brian A. , Bhagunde Pratik , Bell Robert , Penner Natasha , Charil Arnaud , Irizarry Michael C. , Hersch Steven , Reyderman Larisa
Published: January 2025

Background

Lecanemab is a humanized IgG1 monoclonal antibody binding with high affinity to protofibrils of amyloid‐beta (Aβ) protein. In clinical studies, lecanemab has been shown to reduce markers of amyloid in early symptomatic Alzheimer’s disease (AD) and slow decline on clinical endpoints of cognition and function. Herein, a modeling approach was used to correlate amyloid reduction with change in rate of AD progression. This model was then utilized to evaluate amyloid PET as a surrogate marker of efficacy and to assess long‐term effect of lecanemab treatment on CDR‐SB.

Method

Nonlinear mixed‐effects modeling assessed the correlation between amyloid PET and change in CDR‐SB. Data from the lecanemab phase 2 study (Study 201) and Clarity AD (Study 301) were pooled, and CDR‐SB scores were used with beta regression to fit a Richard’s function parameterized in terms of baseline CDR‐SB, intrinsic rate of disease progression, shape, and precision of the beta distribution. Inter‐subject variability was included on baseline CDR‐SB and intrinsic rate. Data from placebo‐treated subjects was used to establish a disease‐progression model; the effect of amyloid reduction on disease progression was defined using data from lecanemab‐treated subjects. Other baseline factors influencing disease progression were explored. Simulations were conducted to evaluate the impact of lecanemab treatment over 4 years.

Result

Richard’s model well‐described AD progression. Baseline CDR‐SB was predicted by diagnosis and baseline mini‐mental state examination (MMSE) score. Intrinsic rate of disease progression was predicted by baseline amyloid PET and baseline MMSE score. Change in amyloid PET was a better predictor of drug effect than lecanemab exposure, demonstrating amyloid reduction as a surrogate marker of clinical efficacy. Simulations projected that the difference in CDR‐SB between lecanemab and placebo treated subjects continued increasing over the entire simulation period. Patients with low amyloid at baseline and less severe disease were projected to have slower disease progression than patients with higher amyloid or more severe disease at start of treatment.

Conclusion

Amyloid reduction was shown to be predictive of slowing of AD progression. Individuals with less advanced disease and lower amyloid baseline were projected to have better outcomes with lecanemab treatment than more advanced patients.
Improving Black/African American Recruitment in ADRD Observational Studies: Black Women Inflammation and Tau Study
Authors: Stradford Joy , Heyworth Nadine , Jackson Michelle , Norman Marc , Thames April , Banks Sarah , Sundermann Erin E.
Published: January 2025

Background

Black/African American women are the most at‐risk demographic group for developing Alzheimer’s disease and related dementias (ADRD). Unfortunately, Black Americans are underrepresented in research, accounting for just 8% of clinical trial participants in the USA. Restrictive study exclusion criteria and medical mistrust are pervasive barriers to research participation in minoritized communities and are often disregarded during the development of a research study. The Black Women Inflammation and Tau Study (BWITS) is an observational study aiming to identify biopsychosocial risk factors for ADRD in Black women to improve health outcomes. Study development was informed by Community‐Based Participatory Research (CBPR) and National Institute on Minority Health and Health Disparities (NIMHD) Research Frameworks to address common participation challenges in minoritized groups.

Method

BWITS is utilizing the CBPR and NIMHD frameworks to design the study and develop culturally informed and effective recruitment strategies. Recruitment is expected to begin in spring, 2024.

Result

Multidisciplinary Team. The study has established a diverse multidisciplinary research team including Black neuropsychologists, neuroscientists, nurse practitioners, and scholars working together to address participants needs.

Community Reciprocity & Partnerships. BWITS strives to establish community reciprocity by providing education outreach to the community and communicating procedures, results, and providing health data to participants. The study team is actively working to build trust through community partnerships with Black community organizations and through routine consultation with a representative Community Advisory Board.

Reducing Barriers. BWITS will use minimally invasive blood draws to study ADRD biomarkers. To minimize time and transportation burden and increase accessibility, BWITS study visits will take place in convenient locations within predominantly Black communities of San Diego and Los Angeles with transportation options offered.

Acknowledging Health Determinants in Minoritized Groups. Diabetes affects 12.1% of Black American adults; however, individuals with diabetes are often ineligible from participating in ADRD studies resulting in disproportionate exclusion. BWITS has adopted broader eligibility criteria to combat this systemic problem.

Conclusion

Understanding and incorporating the lived experiences of special populations should inform the foundation of any research study. The results of study enrollment will illustrate the significance of establishing a thoughtful recruitment plan for Black women research participants.
"Paradoxical” Cerebral Volume Changes in Anti‐Amyloid Immunotherapy Trials
Authors: Fox Nick C , Charil Arnaud , Sachdev Pallavi , Niu Hongmei , Irizarry Michael C. , Hersch Steven , Reyderman Larisa
Published: January 2025

Background

Lecanemab is a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ soluble protofibrils. In two clinical study evaluations of lecanemab, Clarity AD (NCT03887455) and lecanemab phase 2 study (Study 201, NCT01767311), the drug showed statistically significant reduction in disease progression during 18 months of treatment relative to placebo. Anti‐amyloid immunotherapy can result in higher rates of “pseudo‐atrophy” (ie, whole brain volume loss or ventricular enlargement) relative to disease progression observed in placebo‐treated subjects. Herein, we evaluated volumetric MRI changes associated with lecanemab treatment to assess the neurological impact.

Method

Volumetric MRI changes over the duration of the Clarity AD study was compared between placebo and lecanemab‐treated participants (n = 1311). In addition, the association between pseudo‐atrophy and longitudinal changes in tau and amyloid PET were evaluated regionally in a subset of participants in the Clarity AD PET sub‐study (n = 342). The association between volume changes and fluid biomarkers was also investigated.

Result

Volumetric MRI results were inconsistent, with slowing of hippocampal atrophy but greater whole brain volume loss on lecanemab relative to placebo. Volume loss was not associated with worsening in any neurodegenerative biomarkers (plasma NfL, CSF NfL, and t‐tau) or clinical outcomes (CDR‐SB, ADAS‐Cog14, ADCS MCI‐ADL). With disease progression (placebo group), regional atrophy was associated with regional tau accumulation, but was not associated with regional amyloid accumulation. With lecanemab treatment, regional pseudo‐atrophy was associated with amyloid clearance and was not associated with regional tau levels or neuronal loss.

Conclusion

Greater volume loss may be related to reduced amyloid plaques and associated dystrophic neurites as well as inflammation/gliosis. Volume changes are not accompanied with worsening in any neurodegeneration biomarkers and likely do not represent neuronal loss.
Targeting Lrig1 on the surface of Treg cell in the periphery alleviates the symptoms of Alzheimer’s Disease in vivo
Authors: Lee Sang‐Kyou
Published: January 2025

Background

Neurodegenerative diseases, including Alzheimer’s disease (AD), have been long thought to be independent of the peripheral immune system, but their pathogenesis status is functionally influenced by various T cell subsets in the periphery. Especially Treg cells are emerging as an important dynamic population in the brain, but the detailed immunological molecular and cellular processes are poorly characterized

Method

We reported that the cell surface protein Lrig1 is enriched in Treg cells and is an essential regulator of the functions of Treg cells in vitro and in vivo. To evaluate the functional importance of Treg cells in AD pathogenesis, the modulating mAb specific to Lrig1 (GTC 310‐01) via intravenous injection route was administered into 5xFAD or 6xTg mice, the genetic mouse model of AD, and the various AD symptoms were investigated.

Result

GTC 310‐01 significantly improved the cognitive ability of the AD mice, which were analyzed using three different methods (Y‐maze test, passive avoidance test and NOR test). And the level of Ab42 and tau aggregates in AD mice’s hippocampus and cortex areas were substantially reduced by GTC 310‐01 treatment. When the immunological and functional status of T cell subsets in the periphery of the treated animal was evaluated, GTC 310‐01 treatment inhibited the functions of Treg cell. It enhanced gIFN secretion, which increased the permeability of choroid plexus and other BBBs. Thereby, the monocytes in the periphery migrated into the brain and differentiated into active microglial cells and macrophages responsible for clearing the Ab42 and tau aggregates in the brain. After the initial pro‐inflammatory phase after GTC 310‐01 treatment, the number of Treg cells in the brain increased and created the anti‐inflammatory environment to resolve the inflammatory insults.

Conclusion

In conclusion, functional modulation of Treg cells using GTC 310‐01 mAb specific to Lrig1 in the periphery could be a novel therapeutics for treating AD conditions without BBB penetration.
Conditionally Automated Vehicles and Cognitive Challenges: Assessing the Safety of Conditionally Automated Vehicles for Older Adults with Cognitive Challenges
Authors: Hajian Gelareh , Ye Bing , Haghzare Shabnam , Campos Jennifer L. , Mihailidis Alex
Published: January 2025

Background

Driving cessation among people with cognitive impairments (e.g., Mild Cognitive Impairment; MCI) significantly impacts their independence and overall well‐being. Conditionally Automated Vehicles (CAVs) have emerged as a promising solution, potentially extending the safe driving years of at‐risk drivers. However, the safety of using CAVs for individuals with cognitive impairment remains underexplored. Individuals with Subjective Cognitive Decline (SCD; a potential early biomarker for later clinical decline), may also be at‐risk for difficulties managing complex behaviours such as driving. Therefore, this study aims to evaluate the driving performance of older adults with normal cognition, SCD, and MCI to assess their ability to safely transition between automated and manual driving modes using a simulated CAV.

Method

Preliminary data from 17 cognitively healthy older adults, 2 with SCD, and 1 with MCI have been collected. Participants performed conditionally automated driving tasks using a high‐fidelity driving simulator under varied environmental conditions (daytime, nighttime), road geometries (straight, curved), with varying speed limits. A detailed analysis of driving safety, focusing on key metrics such as takeover reaction time and quality (lane centering, steering variation, and acceleration variability) was conducted. A performance baseline was established from the healthy group, segregating them into ‘safe’ and ‘less safe’ categories using a clustering method. The driving performance of participants with SCD and MCI was compared to the control group. By calculating Euclidean distances from cluster centroids we identified the most representative cluster for each individual.

Result

The clustering technique successfully distinguished between ‘safe’ and ‘less safe’ drivers within the cognitively healthy group, outperforming traditional manual methods. This baseline then enabled a comparative assessment for participants with MCI and SCD, demonstrating the ability of our approach to assess whether individuals with SCD and MCI were able to safely perform takeover requests.

Conclusion

This study provides valuable insights into the safety of individuals with cognitive challenges to use CAVs. Our ongoing research aims to expand the participant sample, further explore the relationship between cognitive abilities and driving performance in CAVs, and ultimately develop a methodology to assess and predict the safety of using CAVs for older adults with cognitive impairment.
Analyses of Progressive Supranuclear Palsy Quality of Life in Frontotemporal Lobar Degeneration: Findings from the ALLFTD Consortium
Authors: Nelson Kevin M , Syrjanen Jeremy A. , Forsberg Leah K. , Heuer Hilary W. , Boxer Adam L. , Rosen Howard J. , Boeve Brad F.
Published: January 2025

Background

The Progressive Supranuclear Palsy Quality of Life (PSP‐QoL) scale is a 45‐question participant‐completed questionnaire used to evaluate physical and cognitive task difficulties. Participants enrolled in the ALLFTD research program are asked to complete this questionnaire annually during their study visits.

Method

PSP‐QoL responses were analyzed at baseline visits. Our analysis focused on responses to the overall satisfaction of life (range 0‐100, with 0 being extremely dissatisfied and 100 being extremely satisfied) relative to disease severity (CDR®+NACC‐FTLD global scores) and as a function of clinical phenotypes. A Kruskal‐Wallis test was used to compare overall satisfaction ratings against CDR®+NACC‐FTLD global score.

Result

788 PSP‐QoL survey responses were analyzed (participant mean age 55.3 ±15 years, 50.5% female). Analysis included responses from 372 (47.2%) asymptomatic participants (CN; CDR®+NACC‐FTLD = 0), 140 prodromal (17.8%) CDR®+NACC‐FTLD = 0.5, 160 (20.3%) CDR®+NACC‐FTLD = 1, 106 (13.5%) CDR®+NACC‐FTLD 2, and 10 (1.3%) CDR®+NACC‐FTLD = 3. All symptomatic groups were similar in PSP‐QOL overall satisfaction of life rating: (mean overall satisfaction CDR®+NACC‐FTLD = 0.5: 74.5 (SD 22.5); CDR®+NACC‐FTLD = 1: 74.1 (SD 24.7) and CDR®+NACC‐FTLD = 2/3: 74.1 (SD 25.8)), but these differed from asymptomatic (cognitively normal): (mean 83.7, (SD 14.6); p<0.0001). Similarly, when including the CN group and symptomatic phenotype groups, a statistically significant difference in ratings was seen: mean overall satisfaction CN = 83.7 (SD 14.7), MCI = 78.3 (SD 16.6), PPA = 71.6 (SD 26.9), PSP = 66.3 (SD 28.2), bvFTD = 76.8 (SD 23.8), and other = 70.6 (SD 23.2). However, even after removing the CN group, a difference amongst symptomatic phenotypes remained (p = 0.036).

Conclusion

Mean overall life satisfaction as measured by the PSP QoL questionnaire was lower in all symptomatic compared to clinically normal participants, regardless of disease severity or phenotype. Further longitudinal analyses are needed to better understand how clinical progression impacts overall satisfaction of life.
Identifying the optimal combinations of dementia risk factors to be targeted in multidomain lifestyle intervention in Canada
Authors: Son Surim , Speechley Mark R. , Zou Guangyong , Montero‐Odasso Manuel
Published: January 2025

Background

The optimal combinations of modifiable risk factors to be targeted in preventive dementia trials may vary across countries and settings. We aimed to identify the combinations of modifiable risk factors associated with cognitive change in Canadian adults.

Method

Population Attributable Fraction analyses on 30,097 participants from the Canadian Longitudinal Study on Aging and prevalence of 2, 3 and 4 risk combinations of the 12 modifiable risk factors identified in the 2020 Dementia Lancet report were estimated to note the ten most prevalent combinations. Association between the identified combinations and 3‐year cognitive changes was examined with linear mixed models.

Result

Risk factor combinations were associated with greater change in memory than executive function (Table 1). Among the ten most prevalent dyad combinations, hearing loss and physical inactivity showed the largest adjusted effect on global cognition (β = ‐0.08, 95% CI ‐0.09 to ‐0.06), memory (β = ‐0.1, ‐0.18 to ‐0.14), and executive function (β = ‐0.03, ‐0.04 to ‐0.02). The triad of hearing loss, physical inactivity, and sleep disturbance was associated with the largest adjusted effect across all domains (global: β = ‐0.06, ‐0.07 to ‐0.04; memory: β = ‐0.12, ‐0.15 to ‐0.09; Executive Function: β = ‐0.03, ‐0.04 to ‐0.01). The tetrad of hearing loss, depression, physical inactivity, and sleep disturbance was associated with the largest adjusted effect on memory (β = ‐0.11; ‐0.18 to ‐0.05). The dyad that was associated with greater memory change than their individual effect was hearing loss and physical inactivity, while it was depression, physical inactivity, and sleep disturbance for the triad combination (Figure 1). The tetrad combination included obesity, depression, physical inactivity, and sleep disturbance.

Conclusion

Identifying risk factor clusters with the highest prevalence and potential effect size can optimize efficiency of trial design. Intervention programs should consider including hearing loss and physical inactivity or obesity, depression, physical inactivity, and sleep disturbance. These findings may help strategically tailor multidomain dementia intervention programs to have the greatest impact in the Canadian population.
RoboZen: Humanoid Robots Administer Mindfullness Based Stress Releif Therapy to people with dementia and help them relax and improve mood and cognition
Authors: Khan Arshia A
Published: January 2025

Background

In this study humanoid robots were programmed to deliver mindfulness‐based stress relief therapy to individuals with dementia. Precisely programmed, these robots aim to enhance well‐being, providing tailored interventions for relaxation, mood enhancement, and heightened cognition in dementia care, showcasing technology’s promise in improving overall quality of life [1, 2, 3, 4].

Methods

In this study, the humanoid robot was programmed with a carefully AI based design protocol incorporating calming activities, guided breathing exercises, and interactive engagement, tailored to the cognitive abilities and preferences of individuals with dementia, to effectively deliver mindfulness‐based stress relief therapy.

This mixed‐methods study assessed the effectiveness of humanoid robots in delivering mindfulness‐based stress relief therapy to individuals with dementia. The sample included 9 participants diagnosed with dementia residing in nursing homes. Ethical approval was obtained from the Institutional Review Board.

The intervention involved a humanoid robot delivering mindfulness‐based stress relief sessions. Quantitative data, obtained through pre‐ and post‐intervention assessments, included standardized scales measuring stress levels, mood, and cognitive function. Physiological indicators such as heart rate variability and electrodermal activity were recorded using wearable sensors during sessions.

Qualitative data were gathered through participant observations and post‐session interviews to capture subjective experiences and perceptions of humanoid robot‐administered therapy. Thematic analysis identified recurring patterns and insights.

The study aimed to offer insights into the feasibility, acceptability, and potential benefits of integrating humanoid robots into dementia care for stress relief, contributing to innovative approaches in dementia interventions.

Results

Analysis of data from participants undergoing humanoid robot‐administered mindfulness‐based stress relief therapy showed significant improvements. The Brief Introspection Mood Scale (BMIS) indicated a highly significant enhancement in mood scores post‐intervention. Participants reported consistently positive shifts in emotional states, supported by electrodermal data showing reduced stress levels during and after sessions. Cognitive assessments, using the Montreal Cognitive Assessment (MoCA), consistently demonstrated improved cognitive function following the intervention.

Conclusion

In conclusion, this study demonstrates the promising efficacy of humanoid robot‐administered mindfulness‐based stress relief therapy, revealing significant improvements in mood, physiological stress indicators, and cognitive function among individuals with dementia. This offers a valuable avenue for holistic care interventions.
Born during World War II: Associations with lower incident dementia
Authors: Moza Sotiria , Scarmeas Nikolaos , Yannakoulia Mary , Dardiotis Efthimios , Hadjigeorgiou Georgios M. , Sakka Paraskevi , Kosmidis Mary H.
Published: January 2025

Background

Prior longitudinal studies have found that individuals born during World War II and the postwar period had lower incident dementia (Tom et al., 2020) than previous generations, a finding contradictory to research indicating early‐life stressors as adverse events for late‐life cognition. This study aimed to further explore this association and underlying factors.

Methods

We analysed data from 1063 older Greeks (Dardiotis et al., 2014). Of those, 614 were exposed to WWII during early childhood (≤6 years) (Mean
age = 70.61±2.13, Mean
education = 8.29 years±4.63, 37.50% men) while 349 were not directly exposed (born after 1944) (Mean
age = 66.89±1.37, Mean
education = 11.24 years±5.00, 28.70% men). Participants provided sociodemographic characteristics and medical history (number‐type of comorbidities), and were administered neuropsychological tests (standardised scores were grouped into visuospatial, memory, attention/speed, language, and executive function domains), the Mini Mental State Examination (MMSE) and the Clinical Dementia Rating Scale (CDR). Logistic regressions were performed with the two groups and cognitive variables, using sex, age, education, clinical depression and anxiety, and multimorbidity, as covariates. We also performed chi‐squared tests to compare the two groups’ parental occupations, as indices of prior socioeconomic status.

Results

Individuals exposed to WWII in early childhood outperformed those not‐directly‐exposed, in visuospatial tasks and the MMSE, and exhibited lower scores on the CDR scale, even after adjusting for multimorbidity, and clinical depression and anxiety (Controlling for multimorbidity: Visuospatial perception: B = .538, p = .001, OR:1.713, 95%CI:1.236‐2.374, CDR score: B = ‐2.012, p<.001, OR:.134, 95%CI:.043‐.412, MMSE total score: B = .135, p = .021, OR:1.144, 95%CI:1.020‐1.283, Controlling for depression and anxiety: Visuospatial perception: B = .542, p = .001, OR:1.719, 95%CI:1.240‐2.383, CDR score: B = ‐2.119, p = .001, OR:.120, 95%CI:.035‐.409, MMSE total score: B = .135, p = .021, OR:1.145, 95%CI:1.021‐1.284). Parents in the non‐exposed group were more likely to hold white‐collar jobs than those in the early childhood‐exposed group (mother: χ2
(20) = 41.202, p = .004; father: χ2
(24) = 66.959, p<.001)

Conclusions

Our results parallel the Tom and colleagues’ study (2020), indicating that individuals exposed to WWII‐related stressors demonstrate superior late‐life cognitive performance relative to non‐exposed individuals, even after accounting for covariates. This would suggest the development of cognitive resilience among those exposed to such traumatic events.
Measuring and reporting adherence in multimodal interventions to prevent cognitive decline
Authors: Soldevila‐Domenech Natalia , Ayala‐García Amaia , Forcano Laura , Barbera Mariagnese , Lehtisalo Jenni , Ngandu Tiia , Solomon Alina , de la Torre Rafael
Published: January 2025

Background

Adhering to lifestyle‐based multimodal interventions to prevent cognitive decline is crucial for their success, but limited evidence exists on determinants of adherence. This gap may stem from inconsistent adherence measurement and reporting across studies. Additionally, uncertainties persist regarding the optimal intervention intensity needed for meaningful cognitive benefits. Addressing these gaps is vital for conducting comparative effectiveness research and for the successful implementation of precision prevention interventions. This study aims to present current evidence on determinants of adherence to multimodal interventions, and discuss how to harmonize the assessment of adherence and the reporting of multimodal interventions intensity in World‐Wide FINGER studies.

Method

To identify determinants of global adherence to multimodal interventions, we conducted a systematic search on PubMed and employed snowball methods, involving the pursuit of references within references and electronic citation tracking.

Result

As of January 2024, five studies quantitatively explored factors influencing global compliance or participation with multimodal interventions’ activity programs (Table 1), covering sociodemographic, lifestyle, psychological, cardiovascular, and cognitive factors. However, there was high heterogeneity in compliance reporting; some studies used a 66% completion criterion, while others employed different thresholds (e.g., 40‐50% participation in at least 50% of domains). We argue that using an arbitrary percentage as a compliance cut‐off might not be informative as it depends on the dose delivered and the length of follow‐up; i.e., the intensity of the intervention. We suggest reporting average participation in each intervention component to allow for better cross‐trial comparisons. Additionally, we suggest calculating expected intervention intensity as the ratio between the prescribed dose (number of pre‐specified sessions) and the length (months). Observed intensity could be estimated with the same formula, but correcting the prescribed dose by the average compliance to each intervention component. Lastly, we suggest rating group and individual sessions differently to estimate intervention compliance, and emphasize that global adherence should encompass both compliance and lifestyle change.

Conclusion

Harmonizing adherence reporting in World‐Wide FINGER studies will enhance comprehension of how intervention intensity impacts efficacy. It will also enable pooled analyses to explore adherence determinants, offering valuable insights for designing future precision studies for dementia prevention.
Midlife and old‐age cardiovascular risk factors, educational attainment, and cognition at 90‐years
Authors: Varjonen Anni , Aaltonen Sari , Urjansson Mia , Palviainen Teemu , Saari Toni T , Kaprio Jaakko , Vuoksimaa Eero
Published: January 2025

Background

Cardiovascular (CV) risk factors are associated with increased dementia risk, but their effects on cognition in the oldest‐old (90+) are not well studied. CV risk factors may appear to be protective against dementia due to reverse causation when they are measured during dementia process. To clarify this, we studied CV risk factors measured both at midlife and old age, with 48 years of follow‐up.

Method

We had 96, 90‐97‐year‐olds from the NONAGINTA study consisting of population based older Finnish Twin Cohort study participants born in 1922‐1933. CV risk factors included blood pressure (BP), body mass index (BMI), and physical activity (PA) assessed via questionnaires in 1975, 1981 and 2021‐2023, and cholesterol in 2021‐2023. Telephone‐administered cognitive measures included semantic fluency (1‐minute animal naming), and immediate and delayed recall of three trial 10‐word list learning. We used linear and negative binomial regression analyses (delayed recall) with CV risk factors as independent variables (age, sex, education, and Apolipoprotein E genotype as covariates and adjusted for family data) and 90‐year‐old cognition as a dependent variable.

Result

Those with 7‐11 years and ≥12 years of education had better immediate recall than those with ≤6 years of education (p = 0.003 & p<0.001). Those with ≥12 years (n = 19) of education also scored higher than those with ≤6 years of education both in semantic fluency and delayed recall (p<0.001). Higher middle‐age BMI was associated with better animal fluency (p = 0.011), but not with immediate or delayed recall. Old‐age BMI or cholesterol, and middle‐age or old‐age PA were not related to cognition. Those with high middle‐age BP (n = 6) scored higher in animal fluency (p = 0.005), immediate recall (p = 0.023) and delayed recall (p = 0.003) than those with normal BP. In contrast, those with high old‐age BP (n = 63) scored lower in animal fluency (P = 0.010), but not in immediate or delayed recall.

Conclusion

The most robust finding was that higher (secondary) education is associated with better cognition even in late old‐age. Middle‐age high BP was associated with better old‐age cognition, but this relationship was reversed for old‐age BP. Paradoxical positive effect of high midlife BP may reflect earlier start of BP medication.
Are there trends towards compression of morbidity for dementia? Evidences from four international population‐based cohorts
Authors: Grasset Leslie , Yaqub Amber , Joly Pierre , Ikram M. Arfan , Helmer Catherine , Seshadri Sudha , Beiser Alexa S , Wolters Frank J. , Dufouil Carole
Published: January 2025

Background

Dementia is a major contributor to loss of autonomy in the elderly. Every year spent with dementia results in significant medical and societal costs. Understanding secular trends of life expectancy with and without dementia would enable us to better anticipate future needs. To date, only a few studies have attempted to decipher the scenarios that occurred over the last few decades concerning the life expectancy (LE) with dementia, but heterogeneity in methods hampered comparison of results. A concerted effort for harmonized methods is essential to investigate whether a decline in dementia incidence is also associated with a compression of morbidity, i.e. a lower duration of LE with dementia.

Methods

We leveraged data from four population‐based studies: PAQUID, Three‐City (3C), the Rotterdam Study (RS), and the Framingham Heart Study (FHS). These studies have ascertained dementia cases and vital status over up to 30 years. Five birth cohorts of participants aged 55 years and older were included in the analysis: 1910‐1915, 1915‐1920, 1920‐1925, 1925‐1930, and 1930‐1935. Illness‐death models were used to compute risk of dementia, risk of death among participants with and without dementia, total LE, dementia‐free LE and LE with dementia. We used age as the time scale and models were adjusted for sex.

Results

Results displayed relate to French cohorts. We included 11450 participants, who were dementia‐free at baseline, from both PAQUID and 3C studies (mean age 75 years, 60% female). On average, the follow‐up duration was 11 years and 2003 incident dementia cases were identified. Overall risks of dementia and risk of death decreased by respectively 44% and 47% in participants from birth cohort 1930‐1935, compared to the 1910‐1915 one. From birth cohorts 1910‐1915 to 1930‐1935, total LE at age 70 rose from 16.3 to 20.3 years, and dementia‐free LE rose from 14.2 to 18.5 years. The risk of death among participants with dementia remained stable.

Conclusion

Results from French cohorts showed an increase in dementia‐free LE over 20 years, while LE with dementia remained stable, which indicates a compression of morbidity. We are replicating these analyses in RS and FHS, and will combine results.
Prevalence of modifiable risk factors in cognitive aging cohort participants in Bangkok, Thailand
Authors: Sengpanich Pannita , Thanapornsangsuth Poosanu , Hemachudha Thiravat
Published: January 2025

Background

Dementia poses an escalating socioeconomic challenge, yet evidence suggests potential prevention through proactive correction of risk factors and multidomain interventions. In cost‐conscious Thailand, targeting prevalent risk factors may offer the most feasible strategy for disease prevention, ultimately alleviating healthcare burdens.

Method

Non‐demented participants were consecutively selected from the INDIE cohort, a longitudinal study on cognitive aging at Chulalongkorn University in Bangkok, Thailand. A 40‐minute interview encompassed symptoms, risk factors, social determinants of health, and quality of life. Modifiable risk factors for dementia were identified through an comprehensive literature review (Table 1) and categorized as modifiable at the individual level (e.g., still uncontrolled in the participant) or at the population level (indicating sufficient efforts by the participant). Beyond examining prevalence in the entire cohort, we explored the number of risk factors present in each participant and assessed the impact of correcting these factors on dementia prevention using figures from the Lancet Commission (Livingston, 2020).

Result

Non‐demented participants were consecutively selected from the INDIE cohort, a longitudinal study on cognitive aging at Chulalongkorn University in Bangkok, Thailand. A 40‐minute interview encompassed symptoms, risk factors, social determinants of health, and quality of life. Modifiable risk factors for dementia were identified through an comprehensive literature review (Table 1) and categorized as modifiable at the individual level (e.g., still uncontrolled in the participant) or at the population level (indicating sufficient efforts by the participant). Beyond examining prevalence in the entire cohort, we explored the number of risk factors present in each participant and assessed the impact of correcting these factors on dementia prevention using figures from the Lancet Commission (Livingston, 2020).

Conclusion

This underscores the necessity for healthcare policies targeting dementia prevention, emphasizing modifiable risk factors like low physical activity. While the impact of correcting these risk factors on an individual may seem modest, it can be substantial for those at high dementia risk, particularly when identified through biomarkers. Limitations include a small sample size and non‐generalizable participant selection; future research should extend to rural communities and impoverished urban areas with larger anddiverse samples.
Attitudes and Expectations regarding Dementia Risk Estimation among the General Population in Germany, Spain, and Switzerland
Authors: Baumeister Annika , Hübner Constanze , Gerards Michelle , Cantero‐Fortiz Yahveth , Ribaldi Federica , Sauer Jule , Braun Julia , Boada Mercè , Frisoni Giovanni B , Jessen Frank , Rostamzadeh Ayda , Schwegler Carolin , Schmitz‐Luhn Björn , Woopen Christiane
Published: January 2025

Background

In recent years, research on risk estimation and early detection of Alzheimer’s disease (AD) advanced swiftly. Studies are investigating the likelihood of developing Alzheimer’s dementia (ADD), even during asymptomatic, preclinical, and prodromal stages of AD. Particular hope is pinned on blood‐based biomarkers as these are less invasive than other methods such as lumbar puncture and Positron Emission Tomography (PET)‐scan. Due to the rapid progress of research in this area, it is anticipated that risk estimation measures will be made available to the general population in the future. As part of the PreTAD project (The Predictive Turn in Alzheimer’s Disease: Ethical, Clinical, Linguistic, and Legal Aspects), our objectives were to investigate attitudes and expectations regarding ADD risk estimation in the general population.

Method

We conducted online surveys within the general population (representative quota sample) in Germany (N = 1,000), Spain (N = 1,000), and Switzerland (N = 750). Among others, we assessed aspects influencing decision‐making regarding ADD risk estimation, accepted invasiveness of risk estimation measures, preferred information sources, and expected impact of a hypothetical high risk for ADD.

Result

Preliminary analyses showed that 68% of the German population, 77% of the Spanish population, and 71% of the Swiss population would want to know their risk for developing ADD (rather yes/yes) with a preference for lower invasiveness in all countries (i.e. blood sampling). Physicians were stated as primary information sources regarding risk estimation. Most important aspects influencing decision‐making were existing possibilities to cure or prevent ADD (means > 3,7; 1 = no influence; 5 = strong influence). Individual risk knowledge was rather perceived as a chance to prepare for the future (means > 3.5, 1 = do not agree; 5 = agree) but was also expected to influence feelings of self (means > 3,2) or to cause psychological burden (means > 3,1).

Conclusion

Acceptance for ADD risk estimation, particularly with low invasive measures, seems rather high in Germany, Spain, and Switzerland indicating promising opportunities for the future integration of such strategies into public health initiatives. Physicians, as primary information sources, should carefully consider individual attitudes and expectations regarding ADD risk estimation as risk disclosure may have several psychological and long‐term implications.
Prevalence of Dementia among Malawian adults with HIV and without HIV: A Medical Record Review
Authors: Lee Haeok , Mlombe Yohannie , Song Yeunjoo E. , Choi Yun‐Beom , Yang Hyun‐Sik , Maseke Joseph , Jun Gyungah R , Ngoma Jonathan
Published: January 2025

Background

Malawians, in Sub‐Saharan Africa (SSA), face the double burden of HIV and Alzheimer’s disease and related dementia (ADRD). The life expectancy among HIV‐positive people on antiretroviral therapy has increased consistently over the past 25 years. The purpose of the study was to determine the prevalence of dementia among people living with HIV (PLWHIV) and the general population without HIV as a comparison group in Malawi.

Methods

We conducted a retrospective medical records review of four hundred consecutive patients from a single tertiary health center (200 PLWHIV from the HIV clinic and 200 without HIV from an outpatient clinic) in Lilongwe, Malawi. Since there was no electronic medical records system in Malawi, trained data collectors manually reviewed the medical records based on the instrument devices and the definitions between August 2023 and October 2023. We examined dementia prevalence and clinical characteristics including age, gender, and other clinical history between PLWHIV and the comparison group.

Results

The PLWHIV group was significantly younger than the comparison group (mean age = 44.23±8.07 vs. 57.67±16.28; p<2e‐16), while there was no significant difference in sex (male 55% vs. 50%; p = 0.37). The overall prevalence of dementia was higher in PLWHIV than that in the comparison group (22% vs. 10%; p = 1.4e‐03 before adjusting for age and p = 1.9e‐07 after adjusting for age). Prevalence difference was higher in the older individuals (age>50; 39% vs. 13%; p = 3.2e‐4 before adjusting for age and p = 4.9e‐07 after adjusting for age). Dementia increased with age in both groups: 13% (age<45), 17% (45‐64), and 22% (65 and over), but more rapidly in PLWHIV than in the comparison group (17%, 28% and 50% vs. 5%, 4% and 20% respectively).

Conclusion

This is the first study to demonstrate prevalence of dementia in PLWHIV was significantly higher than that of the general population in Malawi. We confirmed the increased risk of dementia in PLWHIV and provided valuable groundwork for future ADRD research in SSA, specifically in Malawi.