bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between balance, strength and incident dementia in older men: the Health in Men Study
Authors: Trevenen Michelle L , Paterson Jack , Hill Keith , Almeida Osvaldo P , Yeap Bu , Golledge Jonathan , Hankey Graeme , Flicker Leon
Published: December 2023

Background

Increased amount of physical activity has been associated with reduced incidence of dementia. It is less clear whether the discrete physical performance measures of balance and strength are associated with dementia incidence. We investigated whether baseline measures of balance and strength were associated with incident dementia.

Method

A cohort of 1,314 men with no recorded history of dementia, aged 79‐97 underwent physical performance assessments between 2011 and 2013. These assessments were performed during wave 4 of the Health in Men Study, initially recruiting participants 1996‐9 in Perth, Australia. Balance was assessed with a modified Balance Outcome Measure for Elder Rehabilitation (mBOOMER) score: a combination of three tests, the Timed Up and Go, Step and Functional Reach Tests. Strength was tested using knee extension with a spring dynamometer, measured in kilograms. Incident dementia was identified up to December 2017 from the Western Australian Data Linkage System and the national Aged Care Assessment Program. Data were analysed using Cox proportional hazards models. Balance and strength measures were entered as restricted cubic splines to allow for non‐linear relationships. Models were adjusted for sociodemographic, lifestyle and health variables, including hours of physical activity.

Result

A total of 187 (14.2%) incident cases of dementia were identified. Higher (better) mBOOMER scores were associated with decreased risk of incident dementia, with greater changes in risk occurring at higher scores (1 vs 0: HR 0.91, 95% CI 0.81‐1.01, 6 vs 5: HR 0.91, 95% CI 0.81‐1.01, 9 vs 8: HR 0.77, 95% CI 0.70‐0.84, 12 vs 11: HR 0.51, 95% CI 0.37‐0.69). Higher knee extension strength was associated with a decreased risk of incident dementia, with greater changes occurring at lower levels then plateauing at around 25 kilograms (5kg vs 4kg: HR 0.93, 95% CI 0.89‐0.97, 15kg vs 14kg: HR 0.93, 95% CI 0.89‐0.97, 25kg vs 24kg: HR 0.99, 95% CI 0.95‐1.02, 35kg to 34kg: HR 1.00, 95% CI 0.95‐1.06). Relationships remained after excluding those with a dementia diagnosis within two years of baseline physical performance assessment.

Conclusion

Better balance and strength are both associated with decreased risk of developing dementia, thus representing potentially modifiable risk factors.
Caregivers use of technology delivered intervention: The role of computer proficiency
Authors: Thompson Amber , Utz Rebecca , Sparks Catharine , Wong Bob , Iacob Eli , Terrill Alexandra , Caserta Michael
Published: December 2023

Background

Technology delivered interventions are becoming increasingly common as they are considered a cost‐efficient and an effective way to deliver self‐administered education and support to caregivers. These technology‐based interventions have been shown to benefit caregivers by increasing their ability to help cope with caregiver stress. There are also potential challenges associated with technology use such as lack of “meaningful access” to technology systems for some segments of the population (e.g., older adults, individuals of lower socio‐economic status) and usability problems. The purpose of this study is to explore the role of caregiver characteristics and competencies when evaluating the effectiveness of technology‐based interventions.

Method

Time for Living and Caring (TLC) is an on‐line intervention that provides virtual coaching and self‐administered education and resources to caregivers, with the primary goal of helping them schedule and maximize the utility of their respite time. We conducted a pilot test, where Alzheimer’s and related dementia caregivers (n = 159) used the tool for 16 weeks. Our baseline survey of participants employed the Computer Proficiency Questionnaire, or CPQ‐12, to measure various computer proficiencies. This score was then used to investigate differences in overall appraisal of the intervention and self‐reported caregiver outcomes post intervention.

Result

Our findings indicate that CPQ does decrease by age (P>|t| = .000), but that the TLC intervention received favorable reviews despite one’s CPQ score. This includes participant’s self‐perceived benefits, willingness to recommend the intervention to others, and their own willingness to use TLC in the future. It is noted that this sample was highly educated and proficient with technology. This is part selection, given the nature of the study and recruitment strategies. However, these findings also challenge the narrative that older adults are less capable or willing to use on‐line resources.

Conclusion

Overall, computer proficiency was lower among older participants as expected, but computer proficiency was not associated with the evaluation of the intervention or the benefits to caregiver well‐being. Using a design process that focuses on universal design principals, and considers the needs and characteristics of the target population, appears to increase accessibility and usability of technology delivered intervention for caregiver support.
Quantifying tau deposition with the Parametric Estimation of Reference Signal Intensity: a 18F‐PI2620 tau‐PET and 4R‐tauopathy study
Authors: Dilcher Roxane , Taylor Callum , Malpas Charles B , O’Brien Terence , Vivash Lucy
Published: December 2023

Background

Tau positron emission tomography (PET) can detect abnormal tau in neurodegenerative diseases. Conventional reference regions show high PET signal variability and are susceptible to contamination from partial‐volume effects of tracer uptake. The parametric estimation of reference signal intensity (PERSI) has been introduced as a new method to overcome those issues in patients with Alzheimer’s disease. The current study investigates its applicability on patients with underlying 4R‐tauopathy with the radiotracer 18F‐PI‐2620.

Method

In this preliminary, cross‐sectional analysis, 9 patients with clinically suspected 4R‐tauopathy underwent T1‐weighted MRI and 0‐60 min dynamic 18F‐PI‐2620 PET scanning. PERSI identified voxels within the white matter without specific binding for use as a reference region, which was compared with conventional anatomically defined reference regions. Time‐activity curves (TAC) and standardized uptake value ratios in the time window of 20‐40 min (SUVr20‐40) were generated for regions of interest (frontal lobe and globus pallidum). Data was analysed with FSL, PETSurfer, and R.

Result

SUVr20‐40 in the globus pallidum were generally higher than in the frontal lobe for all reference regions (p < 0.001). Frontal lobe, but not globus pallidum SUVr20‐40 were lower when derived from PERSI than when using the cerebellum (p < 0.001) or pons (p < 0.001). When comparing TACs, the PERSI ROI did not show the rapid peak (perfusion) as seen in all other regions (both target and reference), resulting in an overestimation of SUVR in the early phases of the scan. However, activity was the same for all reference regions at later timepoints resulting in similar SUVr20‐40 measures in the globus pallidum.

Conclusion

PERSI derived reference regions do not provide an accurate estimate of early phase perfusion and as such are not appropriate for use as reference regions for reference tissue modelling of PET data. Nonetheless, PERSI provides a suitable reference region for late phase SUVR calculations which is particularly relevant for diseases and tracers were an anatomically defined reference region cannot be easily determined. Future analyses on a larger cohort will determine effect sizes and ROCs to see whether PERSI is a suitable semi‐quantitative investigation to compare between different methodologies and diagnostic groups.
Comparing the Classic Paired Associates Learning Task with a new Smartphone‐Based Version of the Task
Authors: Kaula Alexander J , Taptiklis Nick , Cormack Francesca K
Published: December 2023

Background

PAL is a well‐known and trusted task with good sensitivity to deficiencies in memory capabilities as has been shown in hundreds of studies over the past two decades. There has been considerable interest in a smartphone version of PAL that can be used remotely, and Cambridge Cognition has now completed work on the first production version of this task. Here, we show how the task compares with classic PAL, in an online within‐subjects study. PAL may be used in repeated assessments, and one notable feature is that performance tends to improve most strongly between a first and second attempt at the task. We therefore included a first smartphone ‘Familiarisation’ session on Day One, before the Days Two and Three web and smartphone sessions.

Method

We obtained PAL scores from 76 adults (43m, 33f) aged 50+ (M = 56.3, SD = 5.46) using the Prolific online cognitive testing platform for this three‐day crossover‐design study. Participants were divided into two groups. In a first ‘Familiarisation’ session, all participants used their smartphones to complete a PAL assessment, then on Day Two, one group used the web‐based assessment, and the other used smartphone assessment, and on the last day each group changed device from the previous day’s session, as well as a questionnaire about their experience and comparison of the task in different devices.

Results

We found that test‐retest reliability between the tasks was very good (Pearson’s r > .7) between the first (‘Familiarisation’) session and Day Two, and then excellent (Pearson’s r > .8) between mobile and web devices on Day Two and Day Three of the study. Next, when comparing performance across the two groups (web‐first, and smartphone‐first), bias was not significant and numerically a very small 0.2 adjusted error points. A significant improvement was seen between Familiarisation and Day Two, but not second and third, supporting the value of a familiarisation session.

Conclusion

We found that the new smartphone version is highly comparable to the classic version of the task, and that familiarisation using PAL on smartphone is effective, generalising across both task versions.
Non‐Invasive Temporal Interference Hippocampal Stimulation in Early Alzheimer’s Disease
Authors: Alania Ketevan , Borella Julia , Violante Ines , Martin Evangelia , Rhodes Edward , Butler Christopher R. , Grossman Nir
Published: December 2023

Background

Large‐scale efforts to reverse or stop the progression of Alzheimer’s disease (AD) and associated cognitive decline have failed to produce viable treatment options, highlighting the need for new interventional strategies. A significant feature of AD is aberrant changes in brain network activity and dynamics, closely coupled with functional impairment and pathophysiology in deep brain structures, such as the hippocampus. In this study, we are investigating the effects of multi‐session, non‐invasive temporal interference (TI) electrical stimulation of the hippocampus in early‐stage AD patients. This follows our recent work where we demonstrated the efficacy of TI electrical stimulation to non‐invasively target and modulate activity in the hippocampus of healthy young adults and improve episodic memory performance.

Method

The study consists of transcranial TI stimulation of the hippocampus of 24 early‐stage AD patients daily, in 10 consecutive sessions. We assess the safety and tolerability of the stimulation via questionnaires, interviews and brain scans. Additionally, we explore effects on the pathophysiology and resting state brain dynamics, using a battery of brain imaging modalities: positron emission tomography (PET) of mitochondrial complex‐1, blood oxygen level‐dependent functional magnetic resonance imaging (BOLD fMRI), diffusion tensor imaging (DTI) and arterial spin labelling (ASL). Finally, we explore the effects on cognitive performance using a battery of neurocognitive assessments.

Result

Herein, we will report the outcome of the study’s interim analysis pertaining to safety, neuroimaging and behaviour modulation outcome measures.

Conclusion

Herein, we will report the conclusion of the study’s interim analysis pertaining to safety, neuroimaging and behaviour modulation outcome measures.
Quality of Life in People with Dementia with Lewy Bodies: a think‐aloud study informing economic outcome measurement
Authors: Kinchin Irina , Leroi Iracema
Published: December 2023

Background

Little is known about assessing the quality of life in economic evaluation in people with Dementia with Lewy Bodies (DLB). This study aimed to explore perspectives of people living with DLB, their insights, and preferences for assessing their quality of life with the goal of optimizing shared decision‐making and delivering person‐centred value‐based care that aligns with individual priorities and preferences.

Method

A think‐aloud study, and an associated semi‐structured interview were conducted with people living with dementia, diagnosed, or waiting to receive a formal diagnosis and with the capacity to participate in the research recruited via memory services in Ireland and online support groups. During the interviews, participants were invited to reflect on a ‘good life’ and to ‘think aloud’ while completing four economic quality of life instruments with a perspective that goes beyond health (AD‐5D /QOL‐AD, AQOL‐4D, ICECAP‐O, ICECAP‐SCM). Qualitative data were analyzed using constant comparison.

Result

At the time of submission, 22 think‐aloud interviews had been conducted with people living with dementia of different diagnoses, including 10 interviews with people living with DLB. Preliminary findings indicate that factors such as personal and social relationships, being respected by others, and independence contribute significantly to the overall quality of life of a person living with DLB and evolve as the condition progresses.

Conclusion

Assessing quality of life in people with dementia is methodologically challenging. Economic quality of life instruments with a narrow health focus do not capture all aspects of a ‘good life’ that people living with DLB consider important. Implications of these findings warrant a broader economic quality of life instrument co‐designed with people living with DLB and their care partners.
Exploring the digital divide among immigrant older adults in the United States
Authors: Han Hae‐Ra ,   PLAN trial team
Published: December 2023

Background

The COVID‐19 pandemic has expedited the adoption of digital technology worldwide. Internet use has now become a part of the everyday life for the majority of the United States (US) citizens with over 90% of Americans having access to the internet. Nevertheless, the COVID‐19 pandemic shed a light on an issue of digital equity: the digital divide.

Method

Data for this analysis came from an ongoing, 5‐year multi‐site clinical trial involving community‐dwelling Korean immigrant older adults (65+ years) in the US. Korean older adults represents one of the fastest growing, yet some of the most vulnerable groups in the US due to their limited English proficiency. The primary goal of the trial is to test a community health worker‐led intervention program called PLAN—Preparing health aging through Dementia literacy And Navigation—designed to promote linkage to dementia care among Korean older adults with probable dementia. Potential participants go through cognitive screening using Mini‐Mental State Exam (MMSE) either in‐person or via Zoom to confirm eligibility. Using eligibility screening data, we investigated if mode of MMSE differed by key sociodemographic characteristics such as age, gender, years of education, and ethnic church attendance and cognitive status.

Result

A total of 1,908 Korean older adults were included in the analysis. Nearly two‐thirds (64%) of those who completed MMSE did so in‐person. Logistic regression analysis revealed that age, years of education, and regular church attendance were significantly associated with the either mode of MMSE screening. Specifically, 1‐year increase in age and ethnic church attendance were associated with 5.5% and 1.8 times higher odds of using the in‐person mode (odds ratios = 1.055, p<0.001 and 1.801, p = 0.002, respectively), whereas 1‐year increase in education was associated with 10.9% lower odds of using the in‐person mode (odds ratio = 0.891, p<0.001). Gender and cognitive status were not found significant.

Conclusion

With increasingly intertwined digital and social exclusion in our societies, the findings suggest that Korean immigrant older adults with lower education stay behind in adopting digital technologies such as Zoom. Future research should address ways in which digital literacy can be improved in the vulnerable population.
Relationship between inflammatory markers, compliance to the MIND diet and body composition in older adults without cognitive decline
Authors: Vigil‐Martinez Ana , Salinas‐Contreras Rosa Maria , Martínez‐Galindo Joyce Graciela , Guevara‐Cruz Martha , Pichardo‐Ontiveros Edgar , Sánchez‐Tapia Mónica , León‐Hernández Valeria , Ortiz Ana Luisa Sosa , Torres Nimbe
Published: December 2023

Background

Chronic low‐grade inflammation is one of the main drivers of cognitive decline. The MIND Diet is a dietary pattern that includes foods rich in antioxidants that exert a neuroprotective effect by decreasing oxidative stress (OS) and inflammation. The aim was to evaluate the association between inflammation markers and the intake of foods characteristic of the MIND diet with body composition in older adults.

Method

Cross‐sectional analysis of 73 older adults (70.6±4.6 years, 63% women) without cognitive decline who are participating in the LatAm Fingers study in Mexico. Basal blood samples were taken to determine C‐reactive protein (CRP) and Lipopolysaccharide (LPS). Subjects were divided into two groups according to CRP levels (≤1.0 mg/L without inflammation; >1.0 mg/L with inflammation). Body composition was measured by multi‐frequency bioelectrical impedance (Inbody 720). Participants were asked to autocomplete a validated food frequency questionnaire (POINTER) to evaluate the dietary intake of the MIND diet foods (leafy green vegetables, other vegetables, olive oil, fish, poultry, nuts, whole grains, legumes, and berries). Low adherence was defined as a total score of <8 out of 15 points.

Result

74% of women presented elevated CRP levels (>1.0mg/L). Interestingly, subjects from the group without inflammation had lower values of body mass index (BMI) (27.2 ± 2.4 vs. 30.0 ± 3.6 Kg/m²; p = 0.002), total fat percentage (35.5 ± 5.6 vs. 42.9 ± 6.9%; p = 0.0001) and visceral fat area (108.3 ± 20.7 vs. 123.6 ± 24.0 cm²; p = 0.012) and higher levels of total muscle mass (23.9 ± 5.0 vs. 21.6 ± 4.3Kg; p = 0.049). All participants had metabolic endotoxemia (LPS levels 450 ± 211 ng/mL). Compliance with the MIND diet was deficient (score <8 points) in most participants (58.3%).

Conclusion

High levels of CRP are associated with a negative impact on body composition in older Mexican adults. Additionally, this population is at high risk of cognitive decline as it presents elevated markers of systemic inflammation with a low intake of neuroprotective foods.
Analysis of Tau heterogeneity and proteome‐wide changes in Alzheimer’s Disease at the single‐molecule level
Authors: Guha Sanjib K , Tan Steven , Joly James , Park Deborah , Wang Rosemary , Nortman Brittany , Gillies Taryn E. , Budamagunta Vivek , Robinson Julia K , Rinker Torri Elise , Sherman Jamie , Ellahi Aisha , Wiederhold Thorsten , Kirkpatrick Don , Lipka Johanna , Wendorff Tim , Pandya Nikil J , Rohou Alexis , Kapp Greg , Mallick Parag
Published: December 2023

Background

The molecular heterogeneity of Tau is a critical contributor to Alzheimer’s disease (AD) progression and pathology. Currently, very little is known about the prevalence or impact of the diverse collection of Tau proteoforms. Additionally, individual proteoforms may have different interactions or frequencies within the broader proteome. Here, we detected and analyzed Tau proteoforms in the context of the broader proteome in model systems using a novel single‐molecule proteomic analysis platform with future applicability in AD samples.

Method

We used a single‐molecule proteomic analysis platform that leverages a set of target isoform specific and target PTM specific affinity reagents combined with novel instrumentation, single‐molecule biochemistry, and machine learning bioinformatics to enable deep proteoform and broad proteome analysis. In this study, we first evaluated the proteoform distribution of Tau using commercially available antibody reagents. Proteoform heterogeneity was compared (specifically splicing and phosphorylation variants) in both healthy and diseased samples. Then, total protein counts were assessed across the proteome using Protein Identification by Short‐epitope Mapping (PrISM), which leverages proprietary multi‐affinity probes designed to recognize short epitopes and a machine learning algorithm that decodes binding of hundreds of multi‐affinity probes into protein quantifications.

Result

The approach was evaluated by first measuring defined mixtures of recombinant Tau proteins. Next, we examined Tau enriched from induced pluripotent stem cell (iPSC)‐derived neurons and tau‐expressing cell lines. The platform revealed the molecular heterogeneity of Tau proteoforms missed by bulk measurements and peptide‐centric proteomics approaches. The proteoform data was then supplemented with broader proteome analysis in order to identify proteome‐wide changes – differences in proteins and pathways due to or in combination with specific Tau proteoforms and disease.

Conclusion

Understanding the biology of complex diseases like AD and other Tauopathies depends on understanding both the specific Tau proteoforms that exist at baseline and in disease as well as the pathways and processes impacted in the proteome. Single‐molecule tools that can analyze proteoforms in depth and the proteome broadly and link molecular signatures to disease states are essential. These tools will enable improved biomarkers, improved understanding of disease, and improved therapies for Alzheimer’s disease in the future.
Progress on the Development of the Lewy Body Dementia‐Domain Rating Scale
Authors: Taylor John‐Paul , Boeve Brad F. , Rodriguez‐Porcel Federico E , Kane Joseph PM , Lewis Simon JG , Postuma Ronald B , Quinn Joseph F , Walker Zuzana , Aarsland Dag , Leroi Iracema , Taylor Angela , Ikeda Manabu , Galasko Douglas R.
Published: December 2023

Background

No specific clinical rating scale currently exists for Lewy body dementia (LBD). Clinical rating scales developed for other diseases are therefore used instead for LBD clinical trials. However, these scales are not optimized for LBD and may not sufficiently reflect the complex array of LBD‐related phenomenology, making it more difficult to interpret outcome data from LBD clinical trials.

Method

A working group comprised of 14 members bridging various international LBD‐focused research groups was convened to develop the first iteration of the LBD‐DRS with a focus on inclusion of key LBD related symptom domains, ensuring that any scale is mapped to regulatory expectations, and an emphasis on being patient‐centered. This draft was then subsequently presented to a broader stakeholder group (»50 participants) at the International Lewy body Dementia Conference in June 2022 for further feedback, leading to a further iteration of the scale.

Result

The LBD‐DRS has been designed to capture ratings of the frequency and severity of symptoms across the key domains relevant to LBD – cognitive, neuropsychiatric, motor, autonomic and sleep – as well as the functional impact and perceived burden of symptoms for patients and their care partners. An international Delphi exercise is now planned with many LBD‐relevant stakeholders, which will be coupled with workgroup engagement (for example, with patient‐caregiver groups) to further develop the scale with the resulting final draft anticipated for pilot use in the near future.

Conclusions

In this presentation we will elaborate on the development of the scale, key areas that it will cover as well as challenge points and next steps. Upon completion of the development and refinement of the LBD‐DRS, we propose that this scale will have utility as valid and LBD specific outcome measure in LBD clinical trials.
ATN Cerebrospinal Fluid Biomarkers in Dementia with Lewy Bodies: Initial Results from the United States Dementia with Lewy Bodies Consortium
Authors: Jain Lavanya , Khrestian Maria , Formica Shane , Tuason Elizabeth D. , Pillai Jagan A. , Rao Stephen M. , Oguh Odinachi , Lippa Carol , Lopez Oscar L. , Berman Sarah , Tsuang Debby W , Zabetian Cyrus P , Irwin David J , Galasko Douglas R. , Litvan Irene , Marder Karen , Honig Lawrence S. , Fleisher Jori E , Galvin James E , Bozoki Andrea , Taylor Angela , Sabbagh Marwan , Wint Dylan , Leverenz James B , Bekris Lynn M.
Published: December 2023

Background

Neuropathological hallmarks of AD, amyloid plaques and neurofibrillary tangles, have been described in dementia with Lewy bodies (DLB). Less is known about changes in pre‐mortem cerebrospinal fluid (CSF) amyloid and tau biomarker status in DLB. CSF biomarkers for amyloid (A), tau (T), and neurodegeneration (N) can be utilized to define pre‐mortem pathological status. The overall aim of this investigation was to utilize the ATN research framework to characterize pre‐mortem AD‐related pathology longitudinally in a rigorously characterized cohort of DLB from the Dementia with Lewy Bodies Consortium (DLBC) study. Our hypothesis was that ATN biomarkers would identify DLB with coexistent AD and ATN status would remain the same after 12 months.

Method

Cerebrospinal fluid (CSF) samples from an AD/ADRD cohort were obtained from the Cleveland Alzheimer’s Disease Research Center (CADRC), Cleveland Clinic Lou Ruvo Center for Brain Health Aging and Neurodegenerative Disease Biobank (CBH‐biobank) and DLBC. CSF Aβ40, Aβ42, Aβ42/40 (A), p‐Tau181 (T), and t‐Tau (N), were evaluated. The cohort was subtyped by CSF ATN category and sub‐group of DLB cases were neuropathologically evaluated. A sub‐cohort of DLB cases had longitudinal data with an evaluation at baseline and 12 months later.

Result

DLB patients who were positive for both CSF Aβ42/40 (A+) and p‐Tau181 (T+) remained positive from baseline to 12 months. In contrast, some DLB patients who were positive for CSF Aβ42/40 (A+), but negative for p‐Tau181 (T‐), changed from CSF Aβ42/40 positive to negative at 12 months (p‐value = 0.0153) in the A+T‐N‐ and A+T‐N+ group. Findings from a small DLB subgroup with post‐mortem neuropathologic analyses indicated that most of the cases that were p‐Tau181 positive (T+) also had high Braak stage.

Conclusion

These findings suggest that DLB patients who are positive for CSF Aβ42/40 (A+), but negative for p‐Tau181 (T‐), may have CSF Aβ42/40 levels that can fluctuate over time. In the small DLB subgroup with post‐mortem neuropathologic analysis, there appeared to be a relationship between AD pathologic change and ATN findings that warrants further study in a larger autopsied cohort to fully understand the relationship between ATN status and underlying AD neuropathologic change in DLB.
Associations of Alzheimer’s disease Plasma Biomarkers' and slow wave sleep within Black and White Cognitively Normal Older‐Adults
Authors: Azad Dishari Zaman , White Payton Gabrielle , Cesar Oliver , Kovbasyuk Zanetta , Gonzalez Moses , Wahab Ariana , Mullins Anna E , Kam Korey , Parekh Ankit , Rapoport David M , Ayappa Indu , Jean‐Louis Girardin A , Varga Andrew , Osorio Ricardo S , Bubu Omonigho
Published: December 2023

Background

We studied whether plasma levels of Aβ40, Aβ42, Aβ42/Aβ40, Tau, tau/Aβ42 and NfL are associated with slow wave sleep, and if this association varied within non‐Hispanic Whites and Blacks/African‐Americans.

Method

This was a cross‐sectional analysis of baseline data from 171 cognitively normal older‐adults, volunteering in active NYU studies on memory and sleep. Plasma Aβ40, Aβ42, Tau and NfL were measured using single molecule array (SIMOA). Non‐rapid eye movement sleep (NREM) slow wave sleep (SWS) duration was assessed from 2 nights of in‐lab NPSGs. Associations of NREM SWS duration and plasma AD biomarker levels were examined by applying adjusted generalized linear models and Pearson correlation analysis after data normalization. Analyses were adjusted for age, sex, BMI, race, and education.

Result

Of the 171 subjects (128 Whites and 43 Blacks), 112 (65.5%) were females, and mean (SD) age was 68.6 (6.6) years, BMI was 27.6 (6.1) kg/m**2, and education was 16.9 (2.1). There were no racial differences in age, sex, and BMI, SWS and AHI4%. In comparison to whites, blacks had significantly lower years of education (14.2 vs. 17.2, p <.01). Black/African‐American subjects had significantly lower plasma Aβ40 (248.3 vs. 262.5 pg/ml) and NfL levels (11.4 vs. 15.2 pg/ml). p<.05 for both. There were no significant racial differences in levels of plasma Aβ42, Aβ42/Aβ40, Tau, Tau/Aβ40 and Tau/Aβ42. NREM SWS duration was not associated with plasma Aβ42, Aβ40 or tau in the overall sample. However, in Whites, SWS negatively correlated with plasma Aβ42 (r = ‐0.28, p< = 0.05). In Black/African‐Americans, SWS positively correlated with plasma Aβ42 (r = 0.48, p = 0.05). In Whites, SWS negatively correlated with plasma Aβ40 (r = ‐0.087, p = 0.72), though not significant. In Black/African‐Americans, SWS positively correlated with plasma Aβ40 levels (r = 0.32, p = 0.04). In Whites, SWS negatively correlated with plasma Tau (r = ‐0.153, p = 0.27), though not significant. In Black/African‐Americans, SWS positively correlated with plasma Tau levels (r = 0.52, p = 0.04). NREM SWS was not associated with plasma tau/Aβ42, plasma tau/Aβ40 or plasma NfL in the overall sample and across racial‐subgroups.

Conclusion

Race‐specific relationships between NREM SWS and plasma Aβ42, Aβ40 & Tau might propose differences in SDOH mechanisms that may affect sleep and AD‐risk in older‐adults.
Main lifetime occupational skill and later‐life cognitive function among older adults in the United States, South Africa, India, and Mexico
Authors: Kobayashi Lindsay C , O'Shea Brendan Q , Wixom Caroline , Langa Kenneth M , Weir David R , Lee Jinkook , Wong Rebeca , Gross Alden L.
Published: December 2023

Background

Occupations are a potential source of later‐life cognitive reserve, but it is unknown how lifetime occupational skill level relates to cognitive function amongst older populations across diverse country contexts. We conducted a cross‐national comparison of the associations between main lifetime occupational skill and later‐life cognitive function among men and women living in four economically and socially distinct countries.

Method

Data were from population‐based studies of aging and their Harmonized Cognitive Assessment Protocol (HCAP) sub‐studies in the US, South Africa, India, and Mexico (N = 10,037). Main lifetime occupational skill was classified according to the International Standard Classification of Occupations (ISCO‐2008) in categories of never worked (reference); level 1 (manual labor occupations such as cleaner, construction worker, agricultural worker); level 2 (intermediate occupations such as secretaries, sales assistants, trades workers); and level 3 or 4 (professional or managerial occupations such as teachers, medical practitioners, business owners). Cognitive function was assessed from HCAP measures representing orientation, memory, language, and executive function, standardized to the US population distribution. Sampling‐weighted regression models adjusted for age, minority status, education, and parental education estimated country‐specific associations between main lifetime occupational skill and later‐life cognitive function in men and women.

Result

The mean (SD) age of participants ranged from 68.1 (9.0) years (Mexico) to 76.6 (7.5) years (US; Table 1). Lifetime occupational skill levels varied by country, with the proportion never having worked ranging from 4% (US) to 32% (India), and the proportion with a main lifetime occupation at skill levels 3 or 4 ranging from 6% (India) to 31% (US; Table 1). We observed positive gradients between increasing main lifetime occupational skill and later‐life cognitive function for men and women in the US and Mexico, a positive gradient for women but not men in India, and no association for men or women in South Africa (Table 2; Figure 1).

Conclusion

Main lifetime occupations may be a source of later‐life cognitive reserve, with heterogeneity in this association across countries. While further longitudinal research with more detail on occupations is needed, this study suggests that enriching occupational opportunities in low‐resource global settings may help to promote population cognitive health.
Advancing Engagement and Enrollment of Older Black Americans in Alzheimer’s disease and Dementia‐Related Research
Authors: Cesar Oliver , White Payton Gabrielle , Arthur Matthew , Kovbasyuk Zanetta , Azad Dishari Zaman , Browne Laurel Y , Petersen Karyn , Jean‐Louis Girardin A , Osorio Ricardo S , Bubu Omonigho Michael M
Published: December 2023

Background

The under‐enrollment of racial and ethnic minorities in clinical trials limits the development of culturally tailored disease treatments and preventative strategies. For example, African Americans experience a greater risk of Alzheimer’s disease (AD), yet they remain woefully underrepresented in AD research. This limits understanding of how AD may operate differently in black populations, who have a higher burden of socio‐structural determinants of health. To improve older black American enrollment, The NYU Healthy Brain Aging and Sleep Center (HBASC) team developed a method tailored toward increasing minority enrollment in clinical trials by collaborating with community‐based organizations and minority populations to reexamine barriers to trial participation.

Method

HBASC conducted a single‐site (New York Metropolitan Area) longitudinal study examining sleep and AD in healthy black adults (aged 60‐75). From the study, barriers to trial enrollment were evaluated on a systemic and individual level. The degree to which each level directly or indirectly contributed to barriers to enrollment was further explored using a series of steps and practices seeking to engage underrepresented communities in research. In doing so, team members established and implemented a community‐focused method called FEED. Study personnel demonstrated the feed method by Finding groups, organizations, and trusted community members to collaborate with, Educating community members, Engaging community members through events and educational seminars, and Delivering resources to the community.

Result

Through collaborations with community leaders and organizations, the study team performed community outreach events, raising disease awareness, sustaining trustful relationships, and providing educational resources. The study team saw ∼50% increase in black participant enrollment through the FEED method. Increased engagement in medical research was accomplished when underrepresented communities were empowered with the tools and resources to make knowledgeable decisions.

Conclusion

Diverse populations of patients face complex and multifaceted barriers to enrollment in clinical trials. A FEED framework will help address these barriers at an individual and systemic level.
Sensitivity of NIH ToolBox Motor tests to detect amyloid positivity in cognitively normal older adults
Authors: Persad Carol C , Maher Amanda Cook , Brush David M. , Bross Jordan R , Perrin Cameron K , Fisher Jordan , Murphy YiLu , Koeppe Robert A. , Giordani Bruno
Published: December 2023

Background

Changes in motor functioning and particularly lower motor functioning such as balance and gait have been shown to be an early predictor of dementia (Kueper et al 2017). Based on these results, it has been suggested that balance and gait measures should be a regular component of a clinical dementia risk evaluation. The NIH Toolbox (NIHTB) has developed motor‐based tasks along with its cognitive battery. The aim of this study was to evaluate the utility of several of the NIHTB‐Motor task performance to predict amyloid status in cognitively normal older adults.

Method

Data from 45 cognitively normal adults age 65+ who were part of a larger study examining changes in driving behavior as predictors of cognitive decline were included in this study. Participants were divided into two groups based on PiB PET imaging and amyloid positivity determined using a centiloid scale: values ≥20 were considered positive, values ≤10 were negative; values between 10 and 20 were considered indeterminate and not included (n = 9)). Twenty nine participants were amyloid negative (OCN‐) and 16 were positive (OCN+). Data from the standing balance, grip strength and 2‐minute walking endurance tasks were analyzed using independent sample t‐tests.

Result

There were no differences in age or education between the two groups. However, there was a significant correlation between age and standing balance uncorrected score. As a result, fully corrected scores were used for this analysis. There was a significant difference between the OCN‐ and OCN+ for the fully corrected standing balance standard score (t = 1.7, p<0.04) such that the OCN+ group had lower balance scores compared to the OCN‐ group. No significance differences were found for grip strength or the 2‐minute walking endurance task.

Conclusion

The Standing Balance task from the NIHTB may be a sensitive marker to identify individuals who are at higher risk of developing cognitive impairment and dementia. The NIHTB tasks were designed to be easy to administer in a relatively short amount of time with normative data, and these results suggest the Standard Balance task should be included as a routine measure of dementia risk.
Dementia‐related stigma among health professionals, carers, people living with dementia and the general public in Brazil
Authors: Godoy Carolina , Oliveira Déborah , Ferri Cleusa P
Published: December 2023

Background

People living with dementia (PLWD) often experience stigma and discrimination; however, there is a dearth of research on this topic in middle‐income countries, where the majority of people living with dementia reside.

Method

We conducted a secondary analysis of a database from Alzheimer’s Disease International on the beliefs, attitudes and behavioural intentions towards PLWD among four groups (general public, health professionals, carers and PLWD). We compared the groups using logistic regression adjusted for age, sex and education.

Result

About 33% health professionals believed that dementia is a consequence of natural ageing. When compared to the general public, caregivers (OR = 0.80; CI95%0.65 – 0.97), and healthcare professionals (OR = 0.55; CI95%0.44 – 0.68), were significantly less likely to believe this, regardless of gender, age, and education. Nearly 25% of health professionals believed that communication with PLWD is difficult. Among everyone who agreed with this statement, women compared to men were less likely to have this belief (OR = 0.75; CI95%0.58 – 0.97), and when compared to the general public, health professionals (OR = 0.73; CI95%, 0.58 – 0.92), were less likely to agree with this, regardless of gender, age, and education. Approximately 50% of all participants believed that people do not want to be friends with people with dementia. Those of younger age (OR = 0.98; CI95% 0.97 – 0.99), and health professionals (OR = 0.73, CI95%, 0.57 – 0.94), were less likely to agree with this statement compared to older participants and the general public, respectively. Nearly 45% of the general public believed that it was important to remove responsibilities from the person with dementia so as not to stress them, and carers (OR = 0.50; CI95%, 0.41 – 0.61), were significantly less likely to have such an opinion when compared to the general public, regardless of gender, age, and education.

Conclusion

The proportion of stigma may be even greater than that found, given the high level of education of the participants, which does not represent the general level of education in Brazil. More detailed studies on the stigma related to dementia should be carried out, exploring different scenarios in Brazilian society to better inform societal interventions to reduce dementia‐related stigma.
Brain microRNA‐101 levels influence the risk for Alzheimer’s disease and regulate proteins involved in the disease
Authors: Lahiri Debomoy K. , Wang Ruizhi , Maloney Bryan , Beck John S. , White Fletcher A , Greig Nigel H , Sambamurti Kumar , Counts Scott E.
Published: December 2023

Background

Small non‐coding microRNA (miRNA) play a vital role in regulating various biological and pathological processes, including Alzheimer’s disease (AD), brain injury, and head trauma. AD hallmarks include brain amyloid plaques and neurofibrillary tangles (NFTs). Amyloid plaques are the abnormal aggregation of amyloid‐β peptides (Aβ) derived from Aβ precursor protein (APP), and NFTs consist mostly of hyper‐phosphorylated tau proteins. We have recently shown that miRNAs, such as miR‐20b, miR‐153, and miR‐298, can independently regulate AD‐related protein expression (Wang et al‐Mol Psychiatry‐2022). APOE ε4 increases the risk of AD; however, the role of brain miR101 levels in APOE’s influence is presently unknown. Here, we studied the role of miR‐101‐3p (miR‐101) in AD risk and in regulating levels of critical proteins such as APP, GSK3β, and ECE1 implicated in AD.

Method

Temporal lobes (TL), cerebellum (CB), and posterior cingulate cortices (PCC) were obtained from non‐cognitively impaired (NCI) and AD subjects, and quantitative RT‐PCR measured miR‐101 levels. The target specificity of miR‐101 was tested using dual reporter clones expressing the 3'‐UTRs of either APP, ECE1, or GSK3β mRNAs. Human microglia and differentiated neuroblastoma (SKNSH) cells were transfected with miR‐101 for 72 hours, and cellular RNA, total proteins, and secreted proteins were analyzed by ELISA and Westerns to understand miR‐101‐mediated regulation.

Result

TL and CB regions showed that increased miR‐101 levels were associated with reduced AD risk in the absence of the APOEε4 allele. Interestingly, miR‐101 may increase AD risk in the presence of two APOEε4 alleles. Transfection of miR‐101 altered the translation of several AD‐related proteins, including aggregation‐prone proteins, processing enzymes, and cytokines. Mechanistically, miR‐101 treatment reduced ECE1 and GSK3β mRNA 3’‐UTR activities in reporter clones and protein levels.

Conclusion

We have shown that miR‐101 levels modify AD risk in an APOE allele‐dependent manner. Notably, miR‐101 targets the 3’‐UTRs of ECE1 and GSK3β and reduces their expression, making it a key regulator of AD‐related proteins across species and cell types. Our combined results suggest that miR‐101 is critical in regulating essential proteins relevant to AD pathogenesis and could potentially be a novel “multi‐hit” drug target for AD and other neurodegenerative diseases. NIH grants to DKL and SEC.
Reshaping the path of vascular cognitive impairment with progressive resistance training: A 12‐Month Randomized Trial
Authors: Falck Ryan S , Tam Roger , Dao Elizabeth , Barha Cindy K , Hsiung Ging‐Yuek Robin , Crockett Rachel A , Alkeridy Walid Ahmed , Best John R. , Grant Sofia , Field Thalia S. , Silva Nárlon Cássio Boa Sorte , Brinke Lisanne F Ten , Liu‐Ambrose Teresa
Published: December 2023

Background

Subcortical ischaemic vascular cognitive impairment (SIVCI) is the most common form of vascular cognitive impairment. Importantly, SIVCI is considered the most treatable form of cognitive impairment, due to its modifiable risk factors such as hypertension and diabetes mellitus. Exercise training is a promising intervention to delay the progression of SIVCI, as it actively targets these cardiometabolic risk factors. Despite the demonstrated benefits of resistance training on cognitive function and emerging evidence suggesting resistance training may reduce the progression of white matter hyperintensities, research on SIVCI has predominantly focused on the use of aerobic exercise. Thus, we examined the efficacy of a 12‐month, twice‐weekly progressive resistance training (RT) program on cognitive function in older adults with SIVCI.

Method

We conducted a 12‐month single‐blinded, randomized controlled trial with 91 adults with SIVCI who were randomly allocated to: 1) progressive RT; or 2) balance and tone exercises (BAT; control). Study eligibility included: 1) age 55 years and older; 2) neuroimaging evidence of cerebral small vessel disease at study entry; 3) mild cognitive impairment, as indicated by Montreal Cognitive Assessment scores < 26/30; and 4) the absence of dementia. Measurements occurred at baseline, 6 months, and 12 months. The primary outcome for cognitive function was the Alzheimer’s Disease Assessment Scale‐Cognitive‐Plus (ADAS‐Cog 13 with additional cognitive tests). Gait speed over 4 meters was also assessed as impaired mobility is common among those with SIVCI.

Result

Forty‐five participants were randomized to the RT group and 46 to the BAT group. Mean baseline age was 74.6 years (SD = 5.7 years), 66% of participants were female, and the median Fazekas score was 1. After adjusting for baseline, participants in the RT group had significantly better ADAS‐Cog Plus performance at 12 months vs. BAT (estimated mean difference [RT – BAT]:‐0.20; 95% CI:[‐0.39, ‐0.01]; p = 0.039). In addition, participants in RT had significantly faster gait speed at 12 months vs. BAT (estimated mean difference: ‐0.08 m/s; 95% CI: [‐0.16, 0.00]; p = 0.047).

Conclusion

The prevalence and burden of SIVCI will only increase due to the world’s aging population. Our results suggest progressive resistance training should be considered in the management and treatment of individuals with SIVCI.
Evidence for effect modification by serum clusterin on dendritic cells in association with dementia
Authors: Vivek Sithara
Published: December 2023

Background

Alzheimer’s disease (AD) and AD related dementias (ADRD) are complex heterogeneous diseases with multiple pathogenic mechanisms. Previous experimental studies showed that serum clusterin has a significant role in the maturation of dendritic cells (DCs). Studies showed that myeloid DCs (mDCs) in blood were dysregulated in AD and higher levels of serum clusterin related to higher incidence of dementia. We evaluated the association of DCs in peripheral blood and serum clusterin and their interaction with AD/ADRD.

Method

We used data from 3072 participants in the Health and Retirement Study (HRS) who participated in the 2016 Venous Blood Study (VBS), and had flow cytometry, clusterin and cognition assessed. We used generalized survey logit models to evaluate the association between the DCs, clusterin, and dementia after adjusting for age, sex, race, education, comorbidity, body mass index (BMI) and Cytomegalovirus (CMV) seroprevalence. Utilizing the RNAseq data, we performed differential gene expression (DGE) analysis on DCs, clusterin and dementia to identify overlapping genes in the biological process.

Result

We found that after covariate adjustment, a higher percentage of dendritic cells was associated with lower odds of having dementia (OR = 0.61, 95% CI: [0.44, 0.86]; p = 0.005). We found that higher levels of serum clusterin was associated with higher odds of having dementia. This relationship was somewhat attenuated after covariate adjustment (OR = 1.07, 95% CI [0.99, 1.16], p = 0.09). We found a significant interaction between serum clusterin and DCs in the association with dementia (p = 0.02) with those having low DCs and high clusterin being at increased ADRD risk (OR = 1.25) and those with high DCs and low clusterin being at lower ADRD risk (OR = 0.48) as compared to those who have both low DCs and low clusterin. We identified three genes (TUBB4A, WASHC5 and GSTA4) that were dysregulated in the pathways of DCs and clusterin in association with dementia.

Conclusion

This study has shown, for the first time, an interaction between serum clusterin and DCs in peripheral blood that is associated with increased risk of dementia in a large sample of older adults that needs to be validated in future studies.