bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationships between sleep apnea and insomnia with cognition among Latinos in the National Alzheimer’s Coordinating Center (NACC)
Authors: McKinnon Andrew C , Stickel Ariana M
Published: December 2023

Background

Sleep difficulties (e.g., sleep apnea, insomnia) have been associated with worse late life cognitive health and increased risk for dementia. However, the role of sleep, a potentially modifiable factor, in cognitive aging is understudied among Hispanics/Latinos/Latinxs (henceforth Latinos)—a group that faces dementia disparities. Therefore, we examined the relationships between sleep difficulties and cognition in this population using data from the National Alzheimer’s Coordinating Center (NACC).

Method

Participants included 1,633 Latinos (64% females) ages 21 to 98 years old from the NACC (funded by NIA/NIH Grant U24 AG072122). This analysis used data collected at 35 ADRCs from 2015‐2022. Exposures included history of self‐reported and/or clinically assessed sleep apnea (n = 261) and hyposomnia/insomnia (n = 384). Outcomes were concurrent cognitive scores from tests of learning, memory, semantic fluency, processing speed, confrontation naming, and executive functioning. Covariates included age, sex, education, heritage (e.g., Cuban), cognitive status, and body mass index. General linear models separately tested the associations between sleep difficulties with cognition in crude and fully‐adjusted models. Additionally, we examined whether sex, age, or heritage modified these associations.

Results

Sleep apnea was associated with faster processing speed, and insomnia was associated with worse confrontation naming in crude but not fully‐adjusted models. In fully adjusted models, sex modified the associations of both sleep apnea and insomnia with semantic fluency. Specifically, men without sleep apnea had worse semantic fluency than all other groups; no other group differences emerged. Females in either insomnia group had better semantic fluency than men in either insomnia group, and women without insomnia had marginally better semantic fluency than women with insomnia. Older age (continuous) was associated with worse executive functioning, specifically working memory, among individuals with insomnia to a greater extent than those without insomnia. Heritage did not modify associations between sleep difficulties with cognition.

Conclusion

Consistent with previous, we found that sleep measures were associated with cognition in this group of Latinos from a wide age‐range. Our findings were specific to semantic fluency and varied based on demographic factors (e.g., sex). Future studies should examine the relationships between sleep with longitudinal change in cognition in this underserved community.
The contribution of vascular risk to amyloid and tau PET deposition in middle‐aged adults from the community
Authors: Satizabal Claudia L. , Koijs Daniel , O’Donnell Adrienne , Ghosh Saptaparni , Johnson Keith A. , Beiser Alexa S. , Seshadri Sudha
Published: December 2023

Background

Vascular risk factors during midlife are associated with an increased risk of Alzheimer’s disease (AD). However, it is unclear how exposure to vascular risk factors decades before disease onset contributes to the accumulation of AD neuropathological hallmarks. We aimed to investigate the association of vascular burden with amyloid and tau PET deposition in middle‐aged participants from the Framingham Heart Study (FHS).

Method

We included 376 participants from the FHS Third‐generation cohort (mean age 55.3 ±8.8 years, 53% men) with vascular risk factors and PET imaging (Table 1). Vascular predictors included BMI, HDL cholesterol, systolic blood pressure, use of antihypertensive medication, elevated blood pressure, smoking, and history of diabetes, all derived from the study examination closest to PET. Participants underwent brain PET imaging with Pittsburgh Compound B and Flortaucipir to quantify amyloid and tau, respectively. Our analyses focused on global amyloid (i.e., fronto‐lateral‐retrosplenial composite, FLR) and regional tau (i.e., rhinal and inferotemporal cortices) uptake. Linear regression models were used to assess the association between vascular risk factors and PET outcomes, adjusting for age, age‐squared, sex, PET camera, time between vascular and PET data collection, APOE4 status, and education. We additionally explored interactions with APOE4 status.

Result

Higher HDL cholesterol was related to a lower FLR amyloid deposition (Beta±SE, ‐0.40±0.18, p‐value = 0.026), whereas higher BMI was related to higher inferotemporal tau (0.65±0.31, p‐value = 0.035). Intriguingly, current smoking was associated with lower tau deposition, both in rhinal (‐0.88±0.25, p‐value = 0.001) and inferotemporal (‐0.80±0.23, p‐value = 0.001) cortices (Table 2). We further observed interactions between APOE4 status and smoking on rhinal tau (p‐value = 0.029 for interaction), with significant associations only among non‐e4 carriers (‐0.08±0.53, p = 0.88 in e4 carriers; ‐1.35±0.28, p‐value<0.0001 in non‐carriers).

Conclusion

Our findings suggest vascular risk factors may have an impact on global amyloid and tau deposition in midlife. If confirmed, these results have important implications for early prevention or intervention strategies in AD. Given the reported protective effect of smoking on the incidence of Parkinson’s disease, further analyses are needed to unravel the role of smoking in the accumulation of tau during midlife and the implications in the development of AD.
Helping Carers to Care: feasibility of the 10/66 Dementia Research Group caregiver intervention in rural Benin
Authors: Guerchet Maëlenn , Kouanou Marlène O.G. , Yoro‐Zohoun Inès , Boumédiène Farid , Houinato Dismand S , Preux Pierre‐Marie
Published: December 2023

Background

In sub‐Saharan Africa, the number of people living with dementia is expected to double every 20 years, from 2.7 to 7.6 million. The shortage of trained health professionals leads family members of older people living with dementia to provide informal care. However, lack of knowledge and understanding about dementia leads to difficulties. There is therefore an urgent need to develop interventions to improve the lives of people with dementia and their families in this region. The objective of this study was to determine the feasibility of the Helping Carers to Care (HC2C) caregiver intervention in rural Benin.

Method

This was a before‐and‐after quasi‐experimental study conducted from January to December 2022 in Djidja‐Abomey‐Agbangnizoun, Benin. Two groups of 30 dyad (caregiver / person with dementia) were to receive the intervention in the beginning of the trial or six months later. The intervention consisted of three modules: 1) assessment; 2) basic education about dementia; and 3) training regarding specific problem behaviors. Main outcome measures for caregivers and patients with dementia were assessed at baseline, at 3‐month and at 6‐month. For caregivers, measures included strain (Zarit Burden Interview), psychological distress (SRQ‐20), and quality of life (WHOQOL‐BREF). Dementia participants completed scales assessing behavioral and psychological symptoms (NPI‐Q) and quality of life (DEMQOL).

Result

The study population consisted of 22 elderly people living with dementia and their primary caregiver divided into two groups ‐ control and intervention ‐ of 11 dyads. Both groups were similar with regards to sex, education, marital status, occupation, dementia severity but people in the control group were older. Participation rate was 100% and most of them found the intervention beneficial and advisable to others in the same situation. Full description of the outcomes and group differences at different times will be presented in details.

Conclusion

The need for such intervention among the families of people living with dementia in Benin is obvious. Preliminary results show that implementation is challenging in rural Benin, where dementia awareness is low and care structures are lacking. These results will add to the scarce evidence on feasibility and benefits of caregiver interventions in low‐and middle‐income countries.
Plasma‐based biomarkers of Alzheimer’s Disease in a multi‐ethnic population: A Cross‐Sectional analysis from the WHICAP Study
Authors: Bahl Aanya , Honig Lawrence S. , Kang Min Suk , Sanchez Danurys , Reyes‐Dumeyer Dolly , Lantigua Rafael A. , Dage Jeff L. , Brickman Adam M. , Manly Jennifer J. , Mayeux Richard , Gu Yian
Published: December 2023

Background

Blood‐based biomarkers have the unique potential to make diagnoses along the Alzheimer’s Disease (AD) continuum. The value of these plasma‐based biomarkers in AD among different race and ethnicity, sex, and genetic status groups needs to be evaluated.

Method

The study included 603 participants of the Washington Heights Inwood Columbia Aging Project, a community‐based cohort study. We measured six AD biomarkers, including phosphorylated Tau‐181 (PTau181), total Tau, Amyloid Beta (Aβ) 40, Aβ42, Glial Fibrillary Acid Protein (GFAP), and Neurofilament Light Chain (NfL). We compared the biomarker levels among 95 individuals clinically diagnosed with AD, 167 individuals with Mild Cognitive Impairment (MCI), and 341 cognitively unimpaired individuals using linear regression models, adjusting for age, sex, race and ethnicity, years of education, APOE ɛ4 status, and sample storage time. We further examined whether the association between biomarkers and clinical diagnosis differed by racial and ethnic groups, sex, and APOE ɛ4 status.

Result

The participants were on average 80.23 (SD = 6.77) years old. Participants self‐identified as non‐Hispanic White (24.03%), non‐Hispanic Black (24.70%), or Hispanic (51.21%), with 414 women (68.66%). AD participants had elevated total tau levels (β = 0.303, p = 0.029), NfL (β = 0.472, p <0.001), and GFAP (β = 0.467, p < 0.001) compared to cognitively unimpaired participants. Individuals with MCI also had higher levels of total tau (β = 0.258, p = 0.016), NfL (β = 0.234, p = 0.035), and GFAP (β = 0.248, p = 0.02) than controls. Stratified analyses showed that men with MCI had higher NfL levels than cognitively unimpaired individuals (β = 0.123, p = 0.008). In women, there were no observable differences in NfL levels between individuals with MCI and controls (β = 0.014, p = 0.669). Among APOE e4 carriers, individuals with MCI had higher levels of NfL than unimpaired controls (β = 0.157, p = 0.006). This was not observed in APOE e4 non‐carriers (β = 0.025, p = 0.397).

Conclusion

Consistent with the literature, we found plasma AD biomarkers including total tau, NfL, and GFAP were higher in MCI and AD compared with cognitively unimpaired individuals. Among men and APOE e4 carriers, we found higher NfL levels in MCI individuals than in cognitively unimpaired individuals.
Strategies to inform public policies while studying diverse older adults living alone with cognitive impairment in the United States
Authors: Portacolone Elena
Published: December 2023

Background

Bridging research and policy allows research findings to have a lasting impact in the wellbeing of vulnerable population such as the estimated 4.3 million older adults living alone with cognitive impairment in the United States. For example, a lasting impact comes from healthcare and social services provided by Medicare and Medicaid tailored to address unmet needs of these populations identified via rigorous research. Despite the importance of bridging research with policy, researchers seldom collaborate with policy makers, thus missing the opportunity of influencing policies. Reasons for these limited collaborations include limited knowledge on methods for researchers to collaborate with policy makers. This session will draw from the expertise gained by the research team of the 5‐year Living Alone with Cognitive Impairment Project to involve policy experts in the design of their mixed‐method study.

Method

At the very start of the 5‐year project (2020) we convened a Policy Advisory Group and then conducted 17 one‐on‐one interviews and 4 plenary meetings with its 17 members which include diverse policy experts at national and federal level.

Result

Regular interactions between the research team and the Policy Advisory Group led to: 1) a mixed‐method design aligned with policy priorities; 2) a report highlighting the priorities of PAG members with regard to policies to enhance the wellbeing of older adults living alone in the US; 3) a series of policy briefs highlighting key findings and related policy recommendations.

Conclusion

The oversight, and regular engagement, of a Policy Advisory Group has allowed the Living Alone with Cognitive Impairment Project to focus research activities that are most likely to be translated into policy solutions, thus likely to mostly benefit older adults living alone with cognitive impairment, with emphasis on communities of color. These practices can be easily replicated by researchers in studies supporting underserved populations.
Auditory Gamma Entrainment Leads to Theta Oscillations Asymmetric behavior in both Alzheimer’s Disease and Healthy Participants
Authors: Sedghizadeh Mohammad Javad , Aghajan Hamid , Vahabi Zahra
Published: December 2023

Background

Brain oscillations known for handling various information across brain. The gamma rhythms observed in high‐level cognitive process (Fries et al., Trends in neurosciences 2018) and theta cycle observed to process sensory information and interact with gamma oscillations (Amemiya et al., Cell Reports 2018). Disruption in synchronization of gamma oscillations have been observed in Alzheimer’s disease patients (Uhlhaas et al., Neuron 2006). Gamma stimulation had been shown to reduce the mentioned dysfunction and reported to have therapeutic results (Martorell et al., Cell 2019; Suk et al. Alzheimer’s and Dementia 2020). This study examines the effect of gamma band activity induced by auditory chirp stimulation as a driver for other frequency sources. The chirp signal is designed to entrain 40Hz which had been shown to have therapeutics effects.

Method

33 participants were included in this study including 17 mild AD, 6 MCI and 10 healthy elderlies. A session consists of interleaved periods of forty second stimulation and twenty second silence. The stimulation is a 5kHz tone modulated by a 40Hz chirp at 0.1 duty cycle. EEG data were collected by a 10/20 system. Relative magnitude of the 40Hz oscillations with respect to neighbors’ magnitude during the stimulation was measured as an indicator of the entrained gamma oscillations. Total participants are categorized into entrained and not‐entrained group based on the indicator. Phase locking Value (PLV) is then calculated in theta frequency band.

Result

40Hz entrainment have been observed in healthy participants and also some Alzheimer’s disease patients. Based on the power spectral density (PSD) at forty hertz 23 entrained and 10 not‐entrained participants are separated and PLV analysis have been calculated for the two groups. Theta oscillatory asymmetry have been observed in posterior temporal cortex during auditory stimulation.

Conclusion

Entraining gamma oscillations using auditory stimulation results in cross frequency variation. Phase‐amplitude or phase‐phase coupling measures the simultaneous correlation between specific oscillations. This study suggests that despite the concurrent association of theta‐gamma frequencies, some brain network changes occur in response to gamma oscillation which should be more discussed in related researches.
Executive functioning in low education contexts: evidence from a controlled clinical trial among illiterate adults
Authors: Friedlaender Clarisse Vasconcelos , de Faria Rocha João Victor , dos Santos Tomaz Kelle Luisa , Ruppert Emma Patrice , Lourandes Aida , de Castro Magalhães Assenção Joanna , Grinberg Lea T. , Rosen Howard J. , Rincon Luciana Paula , Ribeiro Norton Gray Ferreira , Constantina Dulce , Zacarias Ana Paula , Caramelli Paulo , Maciel Francisca Izabel Pereira , Resende Elisa de Paula França
Published: December 2023

Background

Education level is a well established modifiable risk factor for dementia prevention. Aiming to improve cognitive reserve and reduce dementia risk in vulnerable populations in Brazil, we created a literacy training program targeting low educated and illiterate adults. In this study, we intend to analyze how executive functioning and cognitive heterogeneity may interfere in the program’s effectiveness.

Method

130 adults attending classes for adult education were screened and 108 met inclusion criteria. The group was divided into control (regular classes, n = 51) and intervention (regular classes + program targeting literacy training) (n = 57). In addition to answering clinical and education history questions, all the subjects underwent an extensive neuropsychological assessment at baseline and at follow up (after six months of intervention), measuring global cognition, executive functioning (EF), memory and language.

Result

77 subjects completed all the assessments at the end of the study. Mean age (years) was 59.0 (±9.17), mean education level (years) 2 (±2.18), 79.2% women and 89.6% Blacks. No significant differences were found between control and intervention groups improvement on reading abilities (reading accuracy of isolated words) at follow up. Considering abandonment reasons of formal education in childhood, subjects with childhood history of learning disability (CHLD) had less improvement on reading abilities at follow‐up. The CHLD group also showed poorer performance on a composite score of EF tasks at baseline (F = 3.814, p = 0.021). EF level at baseline correlated with reading abilities at baseline (Spearman’s rho = 0.659, p<0.001) and follow‐up (Spearman’s rho = 0.703, p<0.001).

Conclusion

Both control and intervention groups showed improvement on reading abilities, regardless of specific literacy training. EF seems to have an impact on reading skills progress. Subjects with CHLD currently display poorer EF and show very little improvement of reading skills, which might indicate an undiagnosed neurodevelopmental disorder (e.g. ADHD, dyslexia, dyscalculia): an uncared condition still harming cognitive reserve improvement to this day. Thus, there is greater risk of developing dementia. Inclusive learning environments must also be considered for low educated populations.
Spiritual Needs of Older Adults Living with Dementia: An Integrative Literature Review
Authors: Britt Katherine C , Boateng Augustine Cassis , Zhao Hui , Ezeokonkwo Francesca , Federwitz Chad , Epps Fayron
Published: December 2023

Background

Providers report that persons living with dementia (PLWD) have greater spiritual needs compared to persons without dementia (Hermans et al., 2017), however, spiritual care for spiritual needs is minimally present in dementia care (van der Steen et al., 2014; Durepos et al., 2017). Encompassing connection, spirituality is positively associated with better health, including cognition, quality of life, sleep, behavioral expressions, and well‐being in older adults (Agli et al., 2015; Britt et al., 2022; Britt et al., 2023; Hosseini et al., 2019). Unmet spiritual needs may lead to depression (Puchalski, 2012), anxiety, and greater physical pain (Delgado‐Guay et al., 2016); thus, addressing the spiritual needs of PLWD is essential to support well‐being and inform personalized care.

Methods

We conducted an integrative literature review to identify the spiritual care needs of PLWD by searching five databases (ATLA Religion, CINAHL, PsychInfo, PubMed, and SocIndex) and identified 12 original research studies that focused on spiritual needs of PLWD, published between 2000‐2022 in English.

Results

Conducted worldwide, included studies comprised PLWD across all stages (mild, moderate, severe) and contained multiple perspectives (PLWD, family, caregiver, healthcare providers, therapists, faith leaders); most studies were in long‐term care (N = 5) and qualitative in design (N = 9). Sometimes described as religious needs, spiritual needs can be individual or in community. Components of spiritual needs included the importance of maintaining connections in relationships and with religious and spiritual rituals and activities (mealtime grace, bedtime prayers, nature, art, music, communion). Supporting the spiritual needs of PLWD includes connecting them to past sources of meaning and supporting their dignity. Facilitating interaction for PLWD with meaningful sources and connections can promote a sense of peace, provide comfort in the loss of ability, help them retain some control, and support their coping mechanisms.

Conclusions

A dimension of holistic care, spiritual care, may facilitate meaningful engagement for PLWD with self and others, supporting their identity and values and leading to a sense of peace. Healthcare providers may utilize complementary, low‐cost holistic care to promote personhood and well‐being among PLWD. Tailored and culturally sensitive spiritual care interventions are needed to support identified spiritual needs among PLWD.
ALLFTD: Identifying and Characterizing Frontotemporal Lobar Degeneration Participants in a Multi‐center North American Study
Authors: Heuer Hilary W. , Forsberg Leah K. , Mester Carly T. , Johnson Noah , Ramos Eliana Marisa , Kantarci Kejal , Kremers Walter K. , Petrucelli Leonard , Rosen Howard J. , Boeve Brad F. , Boxer Adam L. ,   ALLFTD Consortium
Published: December 2023

Background

The ALLFTD (ARTFL‐LEFFTDS Longitudinal Frontemporal Lobar Degeneration) study is an NIH‐funded effort to prepare for clinical trials in sporadic (s‐FTLD) and familial (f‐FTLD) FTLD syndromes by characterizing cohorts, developing new clinical trial outcome measures, and evaluating disease progression. ALLFTD represents the merger and continuation of two prior studies: Advancing Research and Treatment of Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS).

Methods

ALLFTD recruits participants with FTLD spectrum disorders (bvFTD, svPPA, nfvPPA, FTD‐ALS, CBS or PSP), with strong family histories of FTLD, or known FTLD‐associated genetic variants within the family. 26 sites in North America enroll participants for clinical and neuropsychological evaluations, MR Imaging, blood draws, and CSF collection in willing participants; participants are requested to return annually for follow‐up evaluation. All participants are genotyped for dementia‐associated mutations. Participants also enroll in the FTD Disorders Registry for follow‐up surveys. A subset of participants undergo remote assessment via the ALLFTD app. Visits conducted under ARTFL and LEFFTDS are included in the ALLFTD dataset.

Results

ALLFTD has been successful in developing methods to conduct remote or hybrid visits and in actively evaluating participants. Since ALLFTD began in January 2020, 1034 participants (736 new; 298 previously enrolled in ARTFL or LEFFTDS) have been evaluated in the longitudinal arm; an additional 119 participants have been participated in a shortened, biofluid‐focused visit. 349 have returned for follow‐up visits. Including prior participants, the ALLFTD dataset contains 3871 visits from 2343 individuals. 1277 people have sporadic syndromes; 1045 were enrolled as familial. Among s‐FTLD, bvFTD is the most common phenotype (32.8%) followed by PSP (15.9%). 61.4% of f‐FTLD participants were clinically normal at first visit; bvFTD is the most common syndrome in symptomatic f‐FTLD (40%). 477 are confirmed carriers of FTLD‐associated genetic mutations. MRIs were obtained for 2594 visits; 3492 visits have associated blood biospecimens banked; 978 visits have associated CSF samples.

Conclusions

The ALLFTD consortium is actively evaluating participants across North America to better characterize FTLD syndromes and support the planning and development of FTLD clinical trials. Longitudinal datasets including clinical, genetic, and imaging data are available by request.
Translating dementia care to public health: implementation analysis of a community center for people with dementia and family caregivers in Chile
Authors: Gajardo Jean , Aubert Josefina , Moreno Ximena , Aravena Jose M , Navarrete Ignacia , Carcamo Felipe , Abusleme Maria T , Barrientos Carolina , Mascayano Franco
Published: December 2023

Background

As part of the National Plan of dementia in Chile, community centers for people with dementia have been developed (1). This program delivers support to the person living dementia and their family, integrating social and clinical aspects through a multicomponent interprofessional intervention, and has been highlighted as an innovative approach to dementia care (2‐4). There is limited knowledge on implementation aspects influencing its functioning as a public health initiative. This work seeks to analyze implementation outcomes of the first community center, called Kintun, in Santiago, Chile, 2013‐2022.

Method

A qualitative study was conducted following a realistic approach (multiple data collection strategies and informants to analyze complex interventions). Key informants of program implementation were identified to participate in interviews or focus group, at different levels (macro‐level of centralized policy, meso‐level of intervention deliverers and coordinator, and micro‐level of user family caregivers). Table 1 summarizes informants, multiple data collection strategies, and implementation outcomes addressed. Interviews and focus group were audio‐recorded and transcribed. Deductive thematic analysis was used with predetermined codes describing implementation outcomes according to the Active Implementation Frameworks (Blanchard et al, 2017) and implementation outcomes by Proctor et al (2011).

Result

The Kintun program is on a full implementation stage. At a macro‐level, the program has not experienced significant administrative transformations, where fidelity is tensioned due to lack of updated centralized technical orientations. In contrast, at a meso‐level, program components have been locally modified or adapted. Several implementation drivers are identified, such as engagement with the local service network, tailoring according to context, and more recently, the COVID‐19 pandemic, and new policies (explicit health guarantee). The program is highly pertinent for all levels, however, the inception of new health policies challenges its place in the healthcare network.

Conclusion

In the implementation of the first community center for people with dementia in Chile, at a policy macro‐level the program has been continuous and stable. Modifications and adaptations occurred at a meso‐level of implementation, informing of discrepancies in intervention fidelity. Due to the high influence of meso‐level on intervention implementation, it is necessary to explore the implementation processes of other eight centers.
Medial temporal lobe gray matter microstructure alterations provide improved sensitivity to detect neurodegeneration associated with Alzheimer’s disease biomarkers
Authors: Brown Christopher , Das Sandhitsu R. , Xie Long , Nasrallah Ilya M. , Detre John A. , McMillan Corey T , Yushkevich Paul A. , Wolk David A.
Published: December 2023

Background

Despite the strengths conventional structural imaging measures to detect atrophy, cross‐sectional relationships between neurodegeneration and Alzheimer’s disease (AD) biomarkers in early stages is limited. Neurite orientation dispersion and density imaging (NODDI) measures microstructural alterations that are unique from conventional structural metrics. Alterations in microstructure have been detected in individuals with AD compared to cognitively normal individuals, but there is sparse data regarding the relationship between these metrics and AD biomarkers. Here we sought to characterize how NODDI metrics in the medial temporal lobe (MTL) are associated with plasma AD biomarkers.

Method

One‐hundred and sixty‐seven cognitively normal (CN) individuals, 47 individuals with mild cognitive impairment, and 16 individuals with AD underwent diffusion and T1w imaging. T1w images were segmented using the ASHS‐T1 protocol to form anterior and posterior MTL ROIs. Multi‐shell DTI data were collected in 113 non‐collinear directions with 1.5mm isotropic voxels, were pre‐processed using a custom pipeline, and fit with voxel‐wise NODDI models. ANTs was used to linearly register NODDI and T1w images to allow transformation of MTL ROIs to diffusion space. Stepwise‐regression models examined relationships between anterior and posterior MTL NODDI metrics with plasma biomarkers in CN and impaired (MCI/AD) groups after accounting for MTL volume.

Result

NODDI metrics of intracellular volume fraction (icVf) and orientation dispersion index (ODI) were decreased, and isometric volume fraction (isoVf) was increased in cognitively impaired compared to CN. Amyloid positivity was associated with decreased ODI and increased isoVf in cognitively impaired individuals. While posterior MTL volume predicted plasma p‐Tau‐181, inclusion of NODDI metrics subsumed this effect (F‐change>7.54, p<0.0067), and reduced ODI was the best predictor of plasma pTau‐181 within cognitively impaired individuals, while isoVf best predicted pTau‐181 across all individuals. Posterior MTL volume did not predict plasma GFAP, but inclusion of ODI and icVf both significantly predicted plasma GFAP in both CN and impaired individuals (F‐change>12.68, p<.001). Anterior MTL icVf predicted both pTau‐181 and GFAP.

Conclusion

Microstructural alterations measured by NODDI appear more closely linked to AD‐related molecular measures and, thus, may provide a more sensitive cross‐sectional measure of neurodegeneration of the MTL compared to conventional macrostructural metrics.
Variability in prevalence and incidence of dementia and their contributing risk factors by algorithmic classification: Results from the Health and Retirement Study
Authors: Tarraf Wassim , Garcia Marc A , Kuwayama Sayaka , González Hector
Published: December 2023

Background

Studies that use observational population level data with research classification for dementia have to contend with error in classification. Errors might be particularly pronounced in studies examining racial and ethnic disparities in dementia where classification can be confounded by certain risk factors (e.g. Socioeconomic Status; SES).

Method

We use data from the health and retirement study to examine differences in dementia prevalence (in 2000 [n = 6,860] and 2016; [n = 6,892]) and 2‐year incidence (2000‐2002 and 2016‐2018) over two time periods between non‐Hispanic White (NH‐W) and NH‐Black older adults (ages 70+‐years) across 4 algorithmic classifications of dementia in HRS (Langa‐Weir, LASSO, Hurd, and Expert). We then use Oaxaca‐Blinder decomposition techniques to examine the contribution of lifecourse factors (demographic, childhood SES and health, adult SES, and later life health behaviors, and health characteristics) to these racial differences in prevalence and incidence over the two time periods.

Result

All four algorithmic classifications point to consistent differences (favoring NH‐W) in prevalence (Figure 1) and, to a lesser extent, incidence (Figure 2) of dementia. Additionally, dementia prevalence but not incidence decreased, particularly among NH‐B, between 2000 and 2016. Despite these consistent findings, the estimated rates of dementia prevalence and incidence differed depending on the algorithmic choice with the Lange‐Weir classification consistently underestimating rates for NH‐W. Nearly 3/4th of the differences in dementia prevalence between NH‐B and NH‐W were explained by advantageous (among NH‐W) adult SES factors, and later life health behavior, and health characteristics; with SES status consuming the largest share. The contributions of these factors were less notable for differences in dementia incidence.

Conclusion

Assessments of racial disparities in dementia with observational data, where cognitive and physical health and function measures are used to generate research classifications, can lead to varying estimates by choice of algorithm. Sensitivity to algorithmic classification is more notable for dementia prevalence estimates, particularly given SES confounding, than for incidence. Later life health and health behaviors are also notable drivers of racial differences in dementia prevalence. More work is required to calibrate classification techniques to reduce bias and enhance the precision in estimates of magnitude and risks for dementia disparities.
Perceptions of Brain donation and Medical Research Among African American Individuals: Implications for Recruitment and Retention into Alzheimer’s Research
Authors: Starks Takiyah D. , Caban‐Holt Allison M , Cuccaro Michael L. , Ford Tayla , Lloyd Shawnta' , Adams Larry D. , Haines Johnathan L , Reitz Christiane , Vance Jeffery M. , Pericak‐Vance Margaret A. , Byrd Goldie S.
Published: December 2023

Background

African Americans (AAs) are twice as likely to have Alzheimer’s disease (AD) as their White counterparts; yet, this population is largely missing from brain donation research. According to the National Alzheimer’s Coordinating Center, merely 2% of brain donations are obtained from AAs. Medical mistrust among AAs has been well‐documented as a barrier to medical research participation. The purpose of this study was to expand our understanding of AA perceptions of medical research and brain donation.

Method

Using validated survey items, a 35‐item cross‐sectional survey was developed to understand attitudes and beliefs about medical research and brain donation among AAs. Surveys were administered via REDCap (Research Electronic Data Capture) and paper in Florida, New York, North Carolina and Ohio, United States from November 2021 to September 2022. Descriptive analysis of data on research participation and trust in medical research was conducted using SAS® software version 9.4.

Result

A total of 227 AAs participated in this study with about three‐quarters of participants being female. Approximately 90% of AAs reported being born in the US, and nearly half of the sample reported receiving some college education or higher. Only 10.6% of participants reported being very likely to donate their brain to research after death. Despite the low percentage of AAs willing to donate their brain to research, 77.1% had a positive view of medical research and 72.7% trusted researchers in general. In fact, participants perceived that it is “very important” to participate in medical research to help future generations (78.4%), to learn more about AD (66.5%), and receive medical information (56.8%).

Conclusion

Most AAs in this study reported strong trust in medical research and researchers. Medical mistrust may not be a significant barrier to participation in brain donation or AD research for AAs in this sample. Improved health literacy in AD research and brain donation procedures may facilitate engagement of AAs to participate in such research. Findings from this study will be used to inform the development of a culturally relevant health literacy program, with a focus on brain donation and AD research, to enhance opportunities for recruitment and retention of AAs.
The Luci program: a coach‐based online intervention to reduce dementia risk factors
Authors: Lussier Isabelle , Guillemont Juliette , Laroque Flavie M , Bacon Simon L , Boivin Michel , Ferland Guylaine , Lavoie Kim , Paré Guy , Belleville Sylvie
Published: December 2023

Background

A large body of evidence indicates that behavioural interventions on modifiable risk factors for dementia can reduce cognitive decline in at‐risk older individuals. There is growing interest in making such interventions more widely accessible using technology‐based solutions. However, online programs would benefit from incorporating coach‐based interventions, the feasibility of which needs to be demonstrated. Luci is an online, coach‐supported, multidomain lifestyle intervention aimed to improve cognitive health in older adults at risk of cognitive decline. A pilot study was conducted to establish the feasibility of the program.

Method

A web‐App was designed to allow 1‐1 coaching sessions, create and monitor personalized action plans, provide information on brain health, and collect outcome measures. 119 cognitively healthy, community‐dwelling individuals aged 50‐70 with ≥1 lifestyle risk factor (physical activity, diet, cognitive engagement) were recruited in this 24‐week, randomized (Luci vs. wait‐list controls), single‐blind pilot feasibility study. Main eligibility criteria included no severe health conditions (e.g., neurocognitive, psychiatric), to be French‐speaking, available for the duration of the program, and computer literate with access to a device and Internet. Adherence, retention rates, and satisfaction and usability were assessed. Secondary measures included change from baseline in lifestyle risk factors and cognitive performance.

Result

Participants had a mean age of 60.6 (SD = 5.6) and 16.7 (SD = 3.4) years of education; 84.9% were female. Retention and adherence rates were 92.4% and 84.5%, respectively, and a 3.7% difference in attrition rates between the intervention and control groups was observed. Program satisfaction and App usability rates were high, with over 95% agreeing that the coach helped them identify the benefits of and obstacles to changing their lifestyle and respected their opinion. A greater proportion of participants (1.3 to 2.7‐fold) in the intervention versus control group reached a clinically significant change in lifestyle risks. In contrast to the control group, the Luci intervention group showed improvements in cognitive performance.

Conclusion

Providing coach‐based online intervention programs might represent a powerful approach to support durable lifestyle changes in older adults at‐risk for dementia. The results from this study support the Luci program potential as a feasible intervention for effective and sustainable behavioural changes.
Aerobic exercise and volumetric change in the human hippocampus: A meta‐analysis of randomized controlled trials in healthy older individuals
Authors: Balbim Guilherme Moraes , Silva Nárlon Cássio Boa Sorte , Brinke Lisanne F Ten , Falck Ryan S , Hortobágyi Tibor , Granacher Urs , Erickson Kirk I. , Hernández‐Gamboa Rebeca , Liu‐Ambrose Teresa
Published: December 2023

Background

There is promising, albeit equivocal, evidence that aerobic exercise training (AET) increases human hippocampal volume. The evidence is unclear, as recent randomized controlled trials (RCTs) have failed to replicate AET’s previously reported favorable effects on hippocampal volume in cognitively unimpaired older individuals. We thus conducted a meta‐analysis of RCTs investigating the effects of AET on hippocampal volume and cardiorespiratory fitness (CRF) in cognitively unimpaired, healthy older individuals.

Method

A meta‐analysis of RCTs that delivered AET interventions to older individuals. Inclusion criteria were: 1) cognitively unimpaired, healthy individuals aged ≥ 50; 2) AET intervention delivered for at least four weeks; 3) at least one intervention group and one control group; 4) reported data of the effects of AET on hippocampal volume. Two authors independently screened titles, abstracts, and full texts, performed data extraction and methodological quality assessment of included studies. We performed meta‐analyses with random‐effects robust variance estimation models and meta‐regression analyses to test associations between changes in CRF and hippocampal volume. The primary outcome was changes in hippocampal volume, and the secondary outcome was changes in CRF.

Result

Eight parent trials and one secondary outcome article were eligible. The meta‐analytic summary of 17 effect sizes indicated no significant effects of AET on hippocampal volume (SMD = 0.10, 95%CI ‐0.01 to 0.21, p = 0.073). Meta‐analysis of nine studies and effect sizes showed that AET moderately improved cardiorespiratory fitness (SMD = 0.30, 95%CI 0.12 to 0.48, p = 0.005). Improvement in CRF was not statistically associated with changes in hippocampal volume (bSE = 0.05, SE = 0.51, p = 0.923). Methodological quality was poor in one, fair in three, good in four, and excellent in one trial.

Conclusion

AET did not show robust effects on hippocampal volume in cognitively unimpaired, healthy older individuals. Since AET significantly improved CRF, a lack of training fidelity is unlikely to explain our findings. The biologically still plausible favorable effects of AET on hippocampal volume in cognitively unimpaired older individuals might be masked by methodological weaknesses and the inclusion of only nine studies. Future studies need to address: the lack of harmonization of hippocampus quantification methods and insufficient power to detect meaningful changes in hippocampal volume across studies.
Cortical thickness is influenced by bilingual language dominance in typical and pathological cognitive aging
Authors: Grasso Stephanie M , Lucas Fernando Llanos , Petersen Melissa , Downer Brian , Milani Sadaf Arefi , Mehta Neil
Published: December 2023

Background

Prior research in clinical and non‐clinical populations demonstrates that speaking more than one language can modify gray matter structure (e.g., DeLuca et al., 2020; Torres et al., 2022). However, existing work has largely classified bilingualism dichotomously, diminishing the ability to establish associations between bilingual factors (e.g., language dominance) and regional cortical thickness (CT).

Method

We examined cross‐sectional differences in CT across a large, ethnically diverse sample of bilingual and monolingual older adults from the Health and Aging Brain Study: Health Disparities cohort (n = 1,605; O’Bryant et al., 2021). Differences in CT between language dominance subgroups across three levels of diagnostic phase (cognitively unimpaired, mild cognitive impairment (MCI), and Alzheimer’s dementia (AD)) were evaluated using linear‐mixed effects models. Participants were characterized as English‐dominant or Spanish‐dominant speakers according to responses on language interview questions and the Short Acculturation Scale for Hispanics (Marin et al., 1987).

Result

Associations between CT and language dominance differed across diagnostic phase (Tukey‐adjusted ps <0.05). In the cognitively unimpaired group, English‐dominant speakers exhibited greater CT than Spanish‐dominant speakers in in regions‐of‐interest (ROIs) related to auditory processing (Heschl’s gyrus), semantic processing (temporal pole), and executive functioning (frontal pole). Spanish‐dominant speakers exhibited greater CT than English‐dominant speakers in two ROIs supporting motor (precentral) and spatial processing (entorhinal). These CT differences were attenuated in the MCI phase. Here, English‐dominant speakers exhibited greater CT than Spanish‐dominant patients in the frontal pole (executive processing). Spanish‐dominant patients did not exhibit greater CT than English‐dominant patients. Notably, this pattern of group differences was reversed in AD patients. Here, Spanish‐dominant patients exhibited greater CT than English‐dominant patients in ROIs in Alzheimer’s disease‐related regions (parahippocampal and entorhinal).

Conclusion

Our results indicate associations between language dominance and regional CT, with distinct patterns by diagnostic phase. Whereas English‐dominant bilinguals demonstrated greater regional CT relative to Spanish‐dominant bilinguals in the cognitively unimpaired and MCI phase, Spanish‐dominant bilinguals had greater CT in disease‐related regions in the AD phase. The presence of greater CT in Spanish‐dominant bilingual AD patients is suggestive of resistance to pathological progression. Future research examining longitudinal patterns of neural decline in larger samples is needed.
Longitudinal trajectories of myelin loss in the context of Alzhiemer’s disease biomarkers, glial activation, and APOE4
Authors: Stephenson Henry G. , Kohli Akshay , Kecskemeti Steven R , Rubinski Anna , Ewers Michael , Alexander Andrew L , Deming Yuetiva , Ma Yue , Van Hulle Carol A. , Langhough Rebecca E , Jonaitis Erin M. , Dean Douglas C , Ulland Tyler K. , Chin Nathaniel A. , Okonkwo Ozioma , Betthauser Tobey J , Asthana Sanjay , Kollmorgen Gwendlyn , Carboni Margherita , Wild Norbert , Carlsson Cynthia M , Johnson Sterling C , Blennow Kaj , Zetterberg Henrik , Bendlin Barbara B
Published: December 2023

Background

Lower measures of myelin have been associated with abnormal levels of AD biomarkers and APOE4 carriage. However, most human studies have been cross‐sectional, leaving the relationship between AD and myelin changes unclear. The purpose of this study was to determine the association between AD pathology, APOE4, glial activation, and longitudinal changes in quantitative R1 (qR1), a marker sensitive to myelination obtained via MPnRAGE MRI.

Method

Participants from the Wisconsin Registry for Alzheimer’s Prevention (WRAP) and Wisconsin Alzheimer’s Disease Research Center (ADRC) were selected based on available longitudinal MPnRAGE, clinical diagnosis, and APOE genotyping (N = 446). A subset (N = 141) included those with available baseline CSF (AB42/40, pTau181), and gliosis markers (sTREM2, GFAP, YKL40) measured using a robust prototype assay as part of the Roche NeuroToolKit research platform (Roche International). Longitudinal mean qR1 was estimated from white matter regions from the ICBM‐DTI‐81 atlas. In the overall sample, linear mixed effects models predicting regional qR1 (FDR‐corrected) with random intercepts and slopes were estimated controlling for sex, age centered within‐subjects (agec), age averaged within‐subjects (agegm), cognitive impairment, and APOE4 carriage as covariates. Two‐way interactions between impairment and APOE4 with agec were tested in the overall sample as were moderating effects of CSF amyloid‐positivity, pTau181, and gliosis markers on agec in the CSF sample.

Result

In the overall sample, older agec, agegm, and female sex were associated with lower qR1 in a majority of tracts indicating substantial longitudinal declines in qR1 over time and lower qR1 with advanced age and female sex. Sex, impairment, and APOE4 did not show significant agec interactions. Likewise, none of the CSF biomarkers moderated the effect of agec in the CSF subsample.

Conclusion

While aging is robustly associated with longitudinal demyelination as potentially indexed by qR1, these rates do not appear to be moderated by AD pathology, cognitive impairment, APOE4, or glial activation in early disease. Given the capacity for re‐myelination in the context of injury, longitudinal studies are critical for parsing myelin and AD relationships. Established associations between myelin and AD risk may reflect later disease processes, particularly in samples more enriched for tau pathology.