bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between cognition and tau protein deposition measured by PET in subjects with normal cognition and within the Alzheimer’s disease spectrum: A meta‐analysis and systematic review
Authors: Mendez Brahyan J. Galindo , Jagust William J.
Published: February 2022

Background

There is no validated biomarker that has been shown to be useful in the diagnosis and monitoring of AD. Studies using PET have suggested a spatiotemporal relationship between disease progression and higher deposits of beta amyloid and tau‐protein.

Method

Studies investigating cognition and tau protein deposition were searched in databases (PubMed, Cochrane) published in English as of July 2020. Twenty‐five studies of 340 sampled abstracts met inclusion criteria: participants had normal cognition and/or AD/MCI, memory or global composite and tau deposition measured by PET were examined. A meta‐analysis was performed of the correlation coefficients between memory performance and MMSE with tau protein deposition in the temporal lobe and entire cortex. Results of studies examining the relationship using a multivariable statistical approach were extracted for analysis.

Result

Studies were grouped by statistical methodology used. Bivariate correlation analysis and multivariable statistical models were employed to examine the relationship. A meta‐analysis of the correlation coefficient estimating memory performance and tau‐protein deposition in the temporal lobe showed a moderate correlation between higher tau deposition and lower performance on memory tests (r = ‐0.45 (CI ‐0.51; ‐0.39), p = 0.02) across moderately heterogeneous studies (I2= 55%). MMSE and tau deposition in the entire cortex did not consistently correlate across studies with the association reported among a wide range of correlation coefficients (r = ‐0.49 (‐0.65; ‐0.29), I2= 84%). Multivariable models predicting memory performance by tau‐protein deposition in temporal lobe found higher coefficient estimates when the sample was either stratified by beta amyloid load deposition or beta amyloid was included as an interaction. Furthermore, global cognitive composites from retrospective longitudinal cognitive data showed steeper cognitive decline when beta amyloid and tau protein were present.

Conclusion

There is growing evidence supporting the role of tau‐protein as a biomarker that correlates with cognitive and memory decline in AD. There is a spatiotemporal relationship between beta amyloid and tau protein that leads to the development of dementia, which has to be further elucidated. Longitudinal studies will provide a better understanding of tau‐protein aggregation in the brain and its biological interaction with beta amyloid to explain disease progression in AD.
‘If I had dementia, the things that might help me to eat include...’: Exploring findings from a massive open online course.
Authors: Goodwin Isabelle Kate , Lea Emma J , Doherty Kathleen
Published: February 2022

Background

Maximising opportunities to enhance nutrition are a crucial part of providing care to people with dementia, since their risk of malnutrition is increased due to progressive symptoms. A person‐centred approach to eating coupled with skilled caregivers is essential to minimise symptom burden, reduce dependence and maintain quality of life. The aim of this study was to explore perceptions of encouraging eating for those with dementia from responses to a discussion board within a free and openly accessible course: the Understanding Dementia Massive Open Online Course (UD‐MOOC), which asks ‘If I had dementia, the things that might help me to eat include...’.

Method

A total of 3,651 participant discussion responses were collected from 2018 and 2019 course enrolments. Responses were analysed using structural topic modelling followed by secondary thematic analysis to develop meaningful themes to depict participant perceptions.

Result

The majority of participants were female, tertiary educated Australians over 50 years old. One third were paid caregivers. Thirteen topics were isolated from structural topic modelling, from which six major themes were identified: personalised food modifications (such as changes to texture, meal size and frequency of food offered), meal choice (including eating implements and providing food options), meal presentation (including sensory stimulation), eating environment (such as dining and social surroundings), eating assistance (with a focus on independence and encouragement) and end of life nutrition (such as eating safety and perceptions of tube feeding). Meal timing preference was seldom raised.

Conclusion

By exploring perceptions from a discussion board provoking a first‐person stance, participants demonstrated diverse awareness of important aspects to encourage eating in dementia. Furthermore, the opportunity to explore perceived experience provided an understanding of what eating means to caregivers and how they may approach person‐centred eating for people with dementia. In the context of previous research, the findings of this study suggest a gap between perceived best care strategies and practical application of these strategies. This supports the need to nurture opportunities that allow awareness to be implemented in practice and education programs that support current and future dementia caregivers.
Applications of PRESS‐MRS, MEGA‐PRESS, and pCASL to evaluate treatment effect of Kami Guibi‐tang on amnestic MCI
Authors: Jahng Geon‐Ho , Cho Seung‐Yeon , Park Jung‐Mi
Published: February 2022

Background

Kami Guibi‐tang (KGT) is one of the famous herbal medicines used in Asia to treat amnesia, insomnia, loss of appetite, or depression. Previous studies have suggested that KGT could be beneficial for the cognitive functions of AD patients. Therefore, this study aimed to evaluate the therapeutic effectiveness of a 24‐weeks treatment with KGT granules using measurements of brain metabolite and neurotransmitter levels and CBF using a 3T MRI system.

Method

The institutional review board approved this cross‐sectional prospective study. The participants underwent brain MRIs at baseline and after 24 weeks of medication to obtain structural 3D T1‐weighted (3D T1W) image, single‐voxel proton magnetic resonance spectroscopy (1H‐MRS) with TE=35 ms PRESS for quantifying NAA, Cr, Cho, and glutamate complex (Glx), MEscher‐GArwood (MEGA) Point‐RESolved Spectroscopy (PRESS) for quantifying gamma‐aminobutyric acid (GABA), and pseudo‐continuous arterial spin labeling (pCASL) perfusion images.

Result

For MMSE scores, RM‐ANOVA tests showed significantly difference between the KGT and placebo groups (F = 4.71, p = 0.039), not significantly difference between the before and after treatment conditions (F = 0.870, p = 0.358), and no group x condition interactions. For metabolite values and GABA, the GABA+/Cr values were significantly different between the KGT and placebo groups (F = 5.27, p = 0.029). The Glx/Cr values showed a difference trend between the two groups (F = 4.19, p = 0.050) and the group x condition interactions (F = 4.21, p = 0.050). The difference (Diff [%]) in the Glx/Cr values between the before and after treatment conditions were significantly different between the KGT and placebo groups (p = 0.042).

Conclusion

The CBF measure was the sensitive marker to evaluate the treatment effect of KGT on MCI participants. We found that the treatment affected the temporal lobe, including the hippocampus and the fusiform gyrus which are associated with memory. Therefore, further studies should be performed with a relatively larger population and increased dosage.
Atrophy of mammillary bodies in early stages of Alzheimer’s disease
Authors: Tao Alice , Pan Yushan , Myslinski Zachary , Iadecola Costantino , Dyke Jonathan , Chiang Gloria , Ishii Makoto
Published: February 2022

Background

The mammillary bodies (MB) share direct connections with key components of memory circuitry including the hippocampus. Additionally, MB atrophy is present in a number of clinical conditions including late stages of Alzheimer’s disease (AD); however, whether MB atrophy occurs in early stages of AD remains unclear. Voxel‐Based Morphometry (VBM) was conducted to determine whether structural changes to MB are an early feature of AD and to quantify the association between MB atrophy and performance on neurocognitive assessments.

Method

This cross‐sectional study included subjects (n=470) from the Alzheimer’s Disease Neuroimaging Initiative aged ≥ 50 years with volumetric T1‐weighted MR scans at 3 Tesla and cerebrospinal fluid (CSF) AD biomarkers. Normal cognition (cognitively normal, CN, and preclinical AD) was defined as Clinical Dementia Rating (CDR) of 0. Based on previously established criteria, CN subjects (n=112) were negative for CSF AD pathology, while preclinical AD (n=39), early mild cognitive impairment (EMCI, n=108), late mild cognitive impairment (LMCI, n=100), and AD (n=111) subjects were positive for CSF AD pathology. Average grey matter (GM) densities in the MB, hippocampus, and cerebellar vermis were assessed by VBM (SPM12 with MarsBaR toolbox).

Result

GM densities in MB and hippocampi decreased with worsening clinical severity with significant differences beginning in the EMCI stage for both regions. Compared to CN subjects, the relative decrease in GM densities was greater in MB than in the hippocampi in EMCI, LMCI, and AD subjects. Cerebellar vermian GM densities were similar across all groups. Adjusting for age and sex, MB GM densities were associated with CSF levels of amyloid‐β42 (β=0.189, p<0.001) but not with tau or phosphorylated‐tau181 (p>0.05). Hippocampal GM densities were associated with all CSF AD biomarkers (p<0.05). Adjusting for age, sex, and education, MB and hippocampal GM densities were associated with Mini‐Mental State Examination (MB: β=0.270, p<0.001, hippocampi β=0.512, p<0.001) and CDR Sum of Boxes (MB: β=‐0.337, p<0.001, hippocampi: β=‐0.561, p<0.001).

Conclusion

Evidence for MB atrophy was found in early stages of AD and increased with clinical severity, correlating with CSF amyloid‐β42 and neurocognitive measures. These findings support MB atrophy as an early manifestation of AD.
Effects of a 6‐month multicomponent training on lower body function of older adults diagnosed with neurocognitive disorder: Data from Body & Brain Project
Authors: Borges‐Machado Flávia , Barros Duarte Gabriel Moleiro , Ribeiro Oscar , Carvalho Joana
Published: February 2022

Background

Dementia is a leading cause of disability and dependence. It is suggested that exercise has a positive impact on patient’s symptoms and/or disease progression. Nevertheless, to date studies aiming to assess Multicomponent Training (MT) effects on several dementia outcomes show inconsistent results. This quasi‐experimental controlled trial aims to examine the effectiveness of a 6‐month MT intervention on lower body function (e.g., lower body strength and walk speed) of older adults diagnosed with neurocognitive disorder.

Method

40 subjects (N Female: 27) diagnosed with neurocognitive disorder (N Major NCD: 33) selected to participate in a MT Training (Body&Brain Project) were allocated into an exercise group (EG; N: 21; 74.90 ± 5.88 years; age range: 61‐83) or a control group (CG; N:19; 81.74 ± 6.07 years; age range: 70‐89). The EG was submitted to a 6‐month MT intervention (2 sessions per week, 50 minutes per session). Exercise sessions were divided in warm‐up, specific training (e.g., coordination and balance, lower and upper body strength, and aerobics) at light‐to‐moderate intensity, and cool down. The CG group had a monthly recreational session during the same period. 30‐seconds Chair Stand Test and 6‐meters Walk Speed Test, were applied at baseline and post‐intervention to attest respectively, lower body strength and walk speed, as important indicators of lower body function.

Result

Results from ANCOVA test (Table 1), controlled for age, gender and baseline scores, revealed a significant interaction for walk speed test (F (1,35) = 6.61, η2= 0.159, p=0.015) favorable to EG, but not for chair stand test (F (1,30) = 2.129, η2= 0.066, p=0.155).

Conclusion

The 6‐month MT intervention improved walk speed of older adults diagnosed with neurocognitive disorder, which might potentially impact individuals’ daily functionality and reduce the incidence of falls. Future research studies with larger samples are necessary to confirm MT training efficacy on lower body strength. Funding: Portuguese Foundation for Science and Technology: CIAFEL (FCT/UIDB/00617/2020), “Body and Brain” Project (POCI‐01‐0145‐FEDER‐031808), and Ph.D. Grants (SFRH/BD/136635/2018) to FM and [2020.05911.BD] to DB; & IPDJ. Trial Registration: ClinicalTrials.gov ‐ NCT04095962.
Comparison of the sociodemographic and clinical characteristics and level of care home placement in Asian and European people with moderate to severe cognitive impairment living in New Zealand
Authors: Guo Yuxuan Joyce , Rodriguez Claudia Rivera , Cheung Gary , Cullum Sarah , Kerse Ngaire , Martinez‐Ruiz Adrian
Published: February 2022

Background

Due to the ageing population in New Zealand (NZ), there will be more people with dementia in need of long‐term care. As a culturally diverse country, the characteristics of different ethnicities need to be understood in order to provide culturally appropriate care. This study aims to compare: 1) the sociodemographic and clinical characteristics, and 2) the level of care home placement in Asian and NZ European people with moderate to severe cognitive impairment living in long‐term care facilities.

Method

The sample included individuals aged≥65 and self‐identified as Asian or NZ European who had received the Long‐Term Care Facility version of interRAI, a standardised and comprehensive geriatric assessment, in 2018. All participants had moderate to severe cognitive impairment defined by a score of ≥ 3 in the Cognitive Performance Scale (range 0‐6). The analysis examined the association of ethnic group with sociodemographic and clinical variables and level of care home placement.

Result

The sample included 7298 older adults (441 Asians, 6857 NZ Europeans). The average age of the sample was 84.1 SD±8.7 (Asian= 83.7 SD±7.7, European= 84.1 SD±8.8, p=0.29), and 57.5% were female (Asian=62.6%, European=57.2%, p=0.08). Logistic regression showed that, compared with NZ Europeans, Asians were more likely to have untreated diabetes (OR=2.14, 95%CI=1.55–2.96); less likely to be overweight/obese (BMI 25–29: OR=0.54, 95%CI=0.41–0.73; BMI 30–40: OR=0.25, 95%CI=0.13–0.46), have hearing loss (OR=0.55, 95%CI=0.44–0.69) and had fewer medical comorbidities (OR=0.39, 95%CI=0.24–0.65). Despite lower comorbidity, Asians with cognitive impairment were more likely to be placed in hospital level care (OR=1.60, 95%CI=1.23–2.08) and less likely to be placed in dementia level of care (OR=0.53, 95%CI=0.36–0.77).

Conclusion

The study results demonstrate differences in clinical characteristics and level of care home required for Asians and NZ Europeans living in NZ. Despite lower comorbidity, Asians with cognitive impairment were more likely to be placed in hospital level of care and less likely to be placed in dementia level of care. Additional studies are needed to understand this relationship, and the results may help to generate more culturally tailored health services aimed for people with cognitive impairment.
A systematic review of progranulin concentrations in biofluids in over 7,000 people: Assessing the pathogenicity of GRN mutations and other influencing factors
Authors: Swift Imogen J. , Esteve Aitana Sogorb , Heller Carolin , Zetterberg Henrik , Rohrer Jonathan D.
Published: February 2022

Background

Heterozygous mutations in the GRN gene are a major cause of genetic frontotemporal dementia (FTD), accounting for an estimated 5‐10% of all people with FTD. GRN encodes for progranulin, with mutations causing haploinsufficiency, and being associated with significantly lower concentrations of progranulin in biofluids in mutation carriers compared to controls.

Method

We performed a search of the literature (up to December 2019) looking for publications reporting progranulin concentrations within serum, plasma or CSF in any medical condition including FTD and other forms of dementia. We then contacted all authors and asked if they were able to share anonymised data from their study including progranulin concentrations and clinical data including specific mutation if present, clinical diagnosis, age at onset of dementia, sex, and GRN rs5848 polymorphism. Data from 7,071 people was collated and analysed.

Result

Data on plasma progranulin concentrations measured using the Adipogen assay was available from 3,265 cases. Variability in levels across 109 different GRN mutations was seen and when split into mutation groups, missense variants outside the signal peptide had significantly higher levels compared to all other groups, suggesting that these variants are unlikely to be pathogenic. We established a plasma progranulin cut‐off value of 74.8ng/µL between pathogenic GRN mutation carriers and non‐carriers. We found that the GRN rs5848 polymorphism also affected plasma progranulin levels, with the TT genotype associated with significantly lower levels than CC. Sex differences were also seen, with significantly higher progranulin levels in females than males.

Conclusion

Together these findings highlight the variable pathogenicity of different GRN mutations and the importance of considering other factors such as genetic risk factors and sex differences when looking at biofluid concentrations of progranulin. This is of particular relevance in upcoming clinical trials of progranulin‐associated FTD where progranulin levels are being measured as outcome measures.
Unique regional patterns of amyloid burden predict progression to prodromal and clinical stages of Alzheimer’s disease
Authors: Pfeil Julia , Hönig Merle C. , Doering Elena , van Eimeren Thilo , Drzezga Alexander , Bischof Gerard N. ,   Alzheimer's Disease Neuroimaging Initiative
Published: February 2022

Background

Regional differences in amyloid‐beta burden were examined between healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer’s disease (AD) and its prognostic value was compared to other biomarkers.

Method

ADNI data (http://adni.loni.usc.edu/) of four age‐matched amyloid‐beta‐positive groups were included: cognitively stables (CN‐CN, n=38), CN to MCI or AD progressors (CN‐MCI/AD, n=38), MCI stables (MCI‐MCI, n=104), and MCI to AD progressors (MCI‐AD, n=104). Baseline 18F‐florbetapir scans were pre‐processed including normalization and intensity‐standardization (reference: cerebellum). To assess regional differences in amyloid‐beta burden, voxel‐wise group‐wise comparisons (FWE‐corrected) were performed between CN‐CN vs. CN‐MCI/AD and MCI‐MCI vs. MCI‐AD, respectively. Mean amyloid‐beta burden of resulting significant regions was subsequently used in logistic regression analyses together with global amyloid, genetic risk, and CSF biomarkers to determine the best predictive biomarker for progression.

Result

CN to MCI/AD progression was predicted by amyloid deposition in the precuneus, lingual and angular gyrus, pallidum, caudate, middle and superior temporal gyrus. MCI to AD progression was predicted by amyloid deposition in the anterior cingulate gyrus, medial frontal cortex, precuneus, middle and superior temporal gyrus, posterior and anterior insula.

Conclusion

Regional amyloid‐beta burden is a more sensitive predictor of progression to MCI or AD than global amyloid‐beta burden, pointing towards its usefulness as prognostic biomarker.
Maintaining pedagogic excellence in family carer training using online learning
Authors: de Klerk‐Rubin Victoria B
Published: February 2022

Background

The Family Caregiver Course (FCC) is an 18‐week Validation training to sensitize family carers to the psycho‐social needs of their relatives, integrate new behaviors that build relationships and specific verbal and non‐verbal techniques to increase communication. It used: 5 ‘on‐demand’ videos to deliver asynchronous learning with written assignments to process information: 9 synchronous, interactive webinars to process information, practice skills and get coaching; a two‐day in‐person training was used exclusively to practice skills and integrate new behaviors. The book, Validation Techniques for Dementia Care was sent to each participant prior to the class start and a monthly online Support Group is offered to all participants as follow‐up to the course.

Method

Pre‐ and Post‐Surveys of the 2019 FCC (in a partnership between the Alzheimer’s Association of Colorado and the Validation Training Institute) were compared.

Result

After taking this course family carers: reported that they knew what to do when faced with challenging behaviors from their relative; understood that lying or pretending to agree with a disoriented person was not an effective strategy for communication; gained knowledge of the different forms of dementia and that the differences are significant; were clear about the differences between Validation and other methods.

Conclusion

In 2020, VTI again partnered with the Alzheimer’s Association of Colorado for a second iteration of the FCC with 18 family caregivers. Due to COVID – 19 limitations, this course was turned into a completely digital experience. The same learning and skill development inherent in the FCC was delivered through online learning, using principles of online pedagogy. To replace the two‐day in‐person component of this course, we developed four, 4‐hour Zoom sessions that allowed participants to: practice specific Validation techniques, exercise, process and apply what was learned, role play and receive coaching to anchor skills. Important online rules were maintained, such as, offer opportunities for participant engagement every 10 minutes and create a community of inquiry. The outcomes of 2019 and 2020 Pre‐ and Post‐Survey data will be compared in the presentation.
Comparative preclinical evaluation of a microtubule PET tracer with a beta‐amyloid PET tracer in AD mice
Authors: Neelamegam Ramesh , Zhang Wei , O'Boyle Michael , Galvan Veronica , Fox Peter T. , Seshadri Sudha , Kumar J.S. Dileep
Published: February 2022

Background

Currently available PET tracers used in Alzheimer's disease (AD) have limited utility in prognosis and in revealing reliable clinicopathologic correlations of disease. Therefore, identification and validation of novel biomarkers for AD progression and preclinical disease onset through noninvasive neuroimaging is a top priority in biomedical research. We proposed to target microtubules (MTs) as an imaging target for AD in preclinical, postmortem and clinical studies that support the implication of altered regulation of MTs in AD and positively correlated with neurodegeneration process. Furthermore, MT loss in AD is contributed to a large number of mutated proteins, enzymes, and post‐translational modifications compared to other imaging targets. Therefore, targeting brain MTs may be advantageous, as cumulative loss of MTs is the final common pathway for a variety of biochemical pathologies leading to neurodegeneration in AD. [11C]MPC‐6827 is the pioneer BBB‐penetrating PET tracer available for in vivo imaging of MTs in brain.1,2 Herein, we report the comparative binding of [11C]MPC‐6827, and [11C]PiB in Aβ over expressing APP mutated transgenic J20 mice and controls.

Method

[11C]MPC‐6827 and [11C]PiB were synthesized using GE Tracerlab FX2 MEI and FX2N modules. Dynamic PET scans were performed for 30 min after tail vein injection of [11C]MPC‐6827 and [11C]PiB in 6‐month‐old J20 mice and littermates (n=4) using a Siemens Focus 220 microPET scanner. Image analyses were performed with Mango software on reconstructed data.

Result

PET image analyses show ∼30% of reduced whole brain uptake of [11C]MPC‐6827 in J20 mice whereas, [11C]PiB exhibited modest higher binding (∼10%) in J20 than control mice. Standardized uptake values (SUVs) show similar trend of binding of tracers in prefrontal cortex (PFC) and hippocampus in J20 and control mice.

Conclusion

Our preliminary studies show that in J20 mice, binding of the [11C]MPC‐6827 is reduced in whole brain, hippocampus and PFC compared control mice and is inversely correlated with [11C]PiB binding. The effect size of [11C]MPC‐6827 seems higher than [11C]PiB. Therefore, [11C]MPC‐6827 could be used as a PET tracer for human brain imaging of AD and other NDs. Acknowledgement: This work was funded by Center for Biomedical Neuroscience (CBN) 2020‐2021, UT Health San Antonio, Texas, USA.
Alaska Native elders’ cultural beliefs, practices, and values: The case for culturally informed holistic dementia care
Authors: Crouch Maria Christina , Rosich Rosellen M
Published: February 2022

Background

Alaska Native (AN) people are projected to experience Alzheimer’s disease and related dementias at an increasingly high rate in comparison to other US races. However, due to colonization among AN tribes and the subsequent institutionalization of modern medicine, cultural practices and values that greatly impact holistic health and dementia care have been overshadowed and in some instances eradicated. Thus, more can be known about the psychosocial factors that have and can contribute to optimal dementia care for a population that experiences health disparities (e.g., heart disease, chronic lower respiratory diseases, cerebrovascular diseases) and barriers to care (e.g., language, rurality, access to resources).

Method

In order to understand precolonial and present cultural practices that comprise optimal dementia care for AN people, a grounded theory, exploratory study was conducted. Twelve semi‐structured interviews with AN Elders assessed the etiology, course, treatment, caregiving, and the culturally derived meanings of memory function, loss, decline, and disease.

Result

Qualitative analyses revealed eight culturally grounded and salient themes: 1) Traditional Knowledge Systems and Values; 2) Caregiving Networks; 3) Memory Function; 4) AN Spirituality; 5) Stories, Generative Sharing, and Healing; 6) Historical Change; 7) Connection, Communication, and Compassion; and 8) Assisted Living. These themes are best understood through AN lifecycle theory, which is a holistic representation of the culturally specific psychosocial protective factors, disease preventive, and caregiving practices that comprise an AN caregiving model.

Conclusion

This study highlights the overall themes of continuity, connectedness, spirituality, intergenerational transmission, history, and belief systems, which emerged as a result of investigating cultural practices that comprise optimal dementia care for AN people. The culturally adaptive and congruent representations that AN Elder’s utilize in understanding memory functioning, loss, decline, and disease (i.e., forms of dementia) both explain and transcend Western biomedical models. Further, more meaningful beliefs are the outcome of an internalization and lived expression of the AN lifecycle. This AN lifecycle theory provides proscriptions for living life holistically, with a strong connection to land, and provides a fulcrum that allows one to understand the complexity of dementia caregiving as it relates to AN culture, history, and traditions embedded within the current sociocultural context.
Longitudinal associations between racial discrimination and brain aging among black older adults
Authors: Zahodne Laura B. , Sharifian Neika , Kraal A. Zarina , Morris Emily P. , Sol Ketlyne , Zaheed Afsara B. , Meister Lindsey , Mayeux Richard , Schupf Nicole , Manly Jennifer J. , Brickman Adam M.
Published: February 2022

Background

Non‐Hispanic Black older adults exhibit worse brain and cognitive health than non‐Hispanic Whites. Emerging research points to racially‐patterned social stress (e.g., discrimination) as a contributor to racial inequalities independent of socioeconomic and health status. While comparative studies show that non‐Hispanic Blacks face more discrimination than non‐Hispanic Whites, few studies focus exclusively on non‐Hispanic Black older adults in order to examine within‐group heterogeneity and clarify how the unique experiences of discrimination among Black older adults link to their brain aging.

Method

221 non‐Hispanic Black participants in the Washington Heights‐Inwood Columbia Aging Project completed psychosocial measures and structural magnetic resonance imaging (MRI). Experiences of discrimination were operationalized using the Everyday Discrimination and Major Experiences of Lifetime Discrimination scales. After reporting the frequency of discrimination, participants reported the attribution(s) of these experiences (e.g., race). Latent difference score models examined associations between discrimination and brain aging, operationalized as hippocampal and white matter hyperintensity (WMH) volumes measured over an average of four years. Initial models considered general discrimination (i.e., regardless of attribution), and subsequent models considered racial discrimination per sé. All models controlled for age, sex/gender, education, income, total intracranial volume, and length of follow‐up.

Result

General discrimination was not associated with brain aging. Lifetime racial discrimination was associated with lower initial hippocampal volume. Everyday racial discrimination was associated with faster accumulation of WMH over time.

Conclusion

This longitudinal MRI study suggests that racial discrimination may be detrimental for brain aging among non‐Hispanic Black older adults, which could contribute to their disproportionate dementia burden. Disaggregating discrimination by attribution can clarify research on psychosocial contributors to racial inequalities in brain and cognitive aging, as racial discrimination appears to be particularly toxic. Future research should examine both distal (e.g., environmental exposures, life course opportunities) and proximal (e.g., physiological stress pathways, inflammation) mechanisms linking racial discrimination to worse brain aging, which may differ for institutional versus interpersonal forms of racism.
Early engagement with the wider patient community in early‐phase clinical trial design: Insights from the CareRing caregiver community in designing the Brainshuttle AD trial
Authors: Croney Ruth , Agnew David , Vogt Annamarie , Alcaraz Fabien , Svoboda Hanno , Kulic Luka , Proulx Léa
Published: February 2022

Background

Caregivers and families of people with Alzheimer’s disease (AD) play a crucial role in the decision to participate in a clinical trial, and in supporting participants during the trial process. Early engagement with the wider patient community could enable the design of trials that are less burdensome for participants and caregivers. The CareRing initiative gathered caregiver insights on: participant/caregiver motivations for involvement in early phase clinical trials where no treatment benefit is expected; the role caregivers expect to play when loved ones participate in a trial; and holistic support that could help minimize the impact of trial participation on daily life.

Method

Six Roche employees from different geographical regions with varying backgrounds and roles, who are caregivers for a person with AD, participated in two 60‐minute telephone calls. The calls included presentations of the Roche brain shuttle technology and draft protocol for the Phase IB/IIA Brainshuttle AD trial evaluating RO7126209 in prodromal or mild‐to‐moderate AD (NCT04639050), and allowed caregivers to provide input on the protocol and holistic support that could alleviate the burden of participation. Key insights/recommendations from caregivers were used to develop guidance on trial design and supporting materials.

Result

Feedback suggested participants are motivated by being able to help others (including their families) avoid the suffering they experience, decreasing their sense of isolation, and access to state‐of‐the‐art care, testing, and neurology teams. Caregivers noted their participation goes far beyond study visits: they prepare participants for visits physically (e.g. washing, dressing) and mentally (e.g. detailing what visits will involve and supporting anxious or angry loved ones), accompany them on visits, and help participants recover from their change in schedule. Caregivers also carry the psychological burden of providing continual reassurance and being the sole person to answer participant’s questions, particularly until trust is built with the study team, and face challenges in taking time off and re‐organizing appointments where necessary.

Conclusion

Caregiver support and time commitments go far beyond study visits. The guidance provided by caregivers in the CareRing initiative has helped us adapt the design and holistic management of the Brainshuttle AD trial, and co‐create/refine specialized support for both caregivers and participants.
Correlation between MK‐6240 tau‐PET and CSF tau, P‐tau and amyloid proteins
Authors: Gérard Thomas , Malotaux Vincent , Ivanoiu Adrian , Lhommel Renaud , Hanseeuw Bernard J.
Published: February 2022

Background

MK‐6240 is a promising second‐generation tau‐positron emission tomography (PET) tracer for evaluation of cerebral tauopathy in patients with and without cognitive impairment. To further validate the use of MK‐6240 in Memory Clinics, we aimed to evaluate the association between MK‐6240 PET results and well‐validated cerebrospinal fluid (CSF) tau and amyloid protein quantifications.

Method

We acquired MK‐6240 tau‐PET and 3D‐T1 MRI in 44 patients attending our Memory Clinic who accepted lumbar puncture. PET data were processed using PMOD 4.1 Neuro tool: we created three clusters of brain segments based on Braak pathological stages (1‐2; 3‐4 and 5‐6). Standardized uptake value ratio (SUVr) measures were calculated without partial volume correction for these three regions, using cerebellar grey matter as region of reference. SUVr measures in the three regions were correlated to CSF measures of total tau, phospho‐tau 181 (P‐tau) and amyloid (Aβ42) proteins. Linear regressions were calculated for each pair of data.

Result

Table 1 provides the characteristics of the participants, as well as CSF and PET data. Fig. 1‐3 provides illustrative cases. We observed that SUVr significantly correlated with total (t‐tau) and P‐tau levels for each of the three Braak regions, but best correlated for the Braak 3‐4 region (t‐tau: r2=0.184; p=0.004 and p‐tau: r2=0.227; p=0.001, see Fig. 4). Only the Braak 1‐2 SUVr significantly correlated with CSF Aβ42 levels (r2=0.121; p=0.021, Fig. 4, line 3). The SUVr thresholds who best discriminate between CSF t‐tau positive and negative cases (based on our clinical threshold of 381pg/ml) were respectively: 1.54 SUVr (Braak1‐2), 1.35SUVr (Braak3‐4), 1.17SUVr (Braak5‐6).

Conclusion

Amyloid CSF levels only correlated with tau‐PET signal in the Braak 1‐2 region, suggesting an association between these two early pathological processes. In contrast, total and phosphorylated tau CSF levels best correlated with tau‐PET signal in the Braak 3‐4 region, suggesting that tau pathology has to reach the temporal neocortex prior to elevate a “global” tau‐measure such as the one measured in the CSF.
Evaluating the co‐design of a program to supporting living well with dementia
Authors: Bechard Lauren Elizabeth , Wei Cindy , Tupling Olivia , Keller Heather , McAiney Carrie A , Middleton Laura E
Published: February 2022

Background

Engaged research involves stakeholders as active partners in the research process, not just as research participants. Engaged dementia research can improve the relevance and quality of research, empower persons living dementia (PLWD) and family care partners, and acknowledge their expertise gained through lived experience. Conducting engaged research is challenging during COVID‐19 when in‐person interactions are difficult or impossible. The Dementia Lifestyle Intervention for Getting Health Together (DELIGHT) project used an online, engaged research approach to co‐design the DELIGHT program, a 12‐week program to support the health and well‐being goals of PLWD and care partners. Here, we used mixed‐methods to evaluate the DELIGHT co‐design process, its alignment with an Authentic Partnership approach, and experiences, satisfaction, and suggestions for future online co‐design processes.

Method

The DELIGHT project engaged 29 people in the co‐design process during Summer 2020, including PLWD, care partners, service/program providers, healthcare providers, and researchers. The co‐design team met over six, 1.5‐hour online meetings (via Zoom) to develop the program. Although the co‐design process is on‐going, evaluation focused on this first phase of the co‐design process. A 17‐item survey assessed alignment with an Authentic Partnerships approach. Focus groups and interviews used a semi‐structured guide to assess experiences, satisfaction, and suggestions for future on‐line co‐design.

Result

Surveys were completed by 11 co‐design members, and 11 co‐design members participated in interviews or focus groups (not all completed both). Initial analysis of survey results indicates co‐design members felt respected and safe in the co‐design process, felt their perspectives and opinions were valued, and valued the contributions of other members (100% agreed or strongly agreed). All survey respondents felt they gained knowledge and strategies for living well with dementia during the co‐design process. All survey respondents also strongly agreed that the DELIGHT program, when implemented, will have a positive impact on PLWD and care partners. Analysis of interviews/focus groups is ongoing and will be available in Spring 2021.

Conclusion

Co‐design members expressed high satisfaction with the process and felt their experiences were valued and heard. All members expressed a strong belief that the program developed will benefit PLWD and care partners.
Preliminary findings in a platform‐based MCI trial designed to promote adaptive behaviors
Authors: Gibson Allison , Kelly Parsons R , Oaks Dawn C , Pope Caitlin N , Rhodus Elizabeth K , Bardach Shoshana H , Johnson Julia , Barber Justin M , Jicha Gregory A
Published: February 2022

Background

Receiving a diagnosis of mild cognitive impairment (MCI) may lead to experiences of emotional turmoil stemming from a perceived lack of clarity around diagnosis and prognosis. Previous research has identified several maladaptive behaviors resulting from the diagnosis of MCI that may be targeted for intervention in order to help those with a new diagnosis of MCI best adapt behaviors to maintain functional abilities.

Method

A platform‐based MCI trial cohort of individuals, newly diagnosed with MCI from a U.S. Alzheimer’s Disease Research Center, was used to pilot a multicomponent interdisciplinary intervention targeting adaptive behavioral responses to the diagnosis of MCI. Thematic analysis was employed with fifteen focus groups across three study groups of 14 participants. After engaging with each of the platform‐based MCI trial components, participants’ and their study partner’s perceptions of each intervention’s acceptability, satisfaction, and compliance across the multicomponent interdisciplinary intervention were assessed.

Results

Themes that emerged from the data included a preference towards education, learning new information, and skill development. Both persons with MCI and study partners favored intervention components that were novel to them. They also reported higher satisfaction with activities facilitated by a professional (e.g., social worker, physical therapist, or pharmacist) as opposed to intervention activities that were self‐directed. Participants with MCI and their study partners reported those with impairment’s challenges utilizing technology independently, requiring assistance in setting up online medical portals, using wearable exercise trackers and automated pillboxes that represented technology‐dependent components of the intervention.

Conclusion

These data suggest that persons, newly diagnosed with MCI, are interested in adaptive, biopsychosocial interventions for persons with MCI. Acceptability, satisfaction, and compliance may be increased when individuals are engaging in learning novel information and skills that are led and supported by professionals. Assistance with and or training in the use of technology‐based interventions may be needed to maximize the impact of such approaches. Further studies exploring the impact on the cognitive and functional decline that may be mediated by adaptive behavioral interventions in persons newly diagnosed with MCI are warranted.
The interaction of APOE genotype and amyloid‐β PET predicts PET but not CSF measures of tauopathy in regions of high APOE mRNA expression
Authors: Dincer Aylin , Chen Charles D. , McKay Nicole S. , McCullough Austin A. , Flores Shaney E. , Keefe Sarah J. , Schultz Stephanie A. , Feldman Rebecca L. , Hornbeck Russ C. , Cruchaga Carlos , Holtzman David M. , Morris John C. , Benzinger Tammie L.S. , Gordon Brian A.
Published: February 2022

Background

The apolipoprotein E (APOE) ε4 allele is the most well‐established genetic risk factor for late‐onset Alzheimer disease (AD). The ε4 allele is strongly linked with cerebral β‐amyloidosis whereas its relationship with tauopathy is less established. Here we investigate the relationship between APOE ε4 carrier status, regional amyloid‐β‐ (Aβ) and tau‐ positron emission topography (PET), APOE mRNA expression patterns, and cerebrospinal fluid phosphorylated tau (CSF ptau).

Method

350 participants from the Knight Alzheimer Disease Research Center (mean age = 69.7) underwent tau‐PET ([18F]‐flortaucipir) and Aβ‐PET ([18F]‐florbetapir) imaging. Tau‐ and Aβ‐ PET data were converted to standardized uptake value ratios (SUVRs). APOE ε4 carrier status was defined by the presence of at least one ε4 allele. CSF ptau data was available for 270 of the participants. Linear regression models were used to predict regional Aβ‐ and tau‐PET levels from APOE ε4 carrier status. Additional models were used to predict regional tau‐PET and CSF ptau from the interaction of APOE genotype and global Aβ‐PET. Age and sex were included as covariates in all models. Regional APOE mRNA expression was derived from the Allen Human Brain Atlas (Fig. 3G).

Result

Strong associations were found between elevated regional tau‐ and Aβ‐ PET levels and APOE ε4 carrier status (Fig. 1A, B). There was a significant interaction between APOE genotype and global Aβ‐PET predicting tau‐PET levels specifically in the entorhinal, amygdala, and superior temporal regions (Fig 1C), but not CSF ptau (Fig. 2). The spatial pattern of APOE mRNA expression was significantly associated to the spatial pattern of APOE ε4 genotype exerted on regional tau‐PET, but less so for regional Aβ‐PET (Fig. 3).

Conclusion

APOE ε4 genotype exerts influence on tauopathy above its effect on Aβ. These effects occur in regions of the brain that have high APOE mRNA expression, suggesting potential local tissue vulnerability to tauopathy. The lack of an interaction in CSF ptau may be due to different roles soluble and aggregated forms of the tau protein play in AD pathophysiology.
Sex differences in brain aging among adults with APOE4 genetic risk and family history of Alzheimer’s disease
Authors: Subramaniapillai Sivaniya , Rajagopal Sricharana , Snytte Jamie , Otto Ross , Einstein Gillian , Rajah Natasha ,   the PREVENT‐AD Research Group
Published: February 2022

Background

Determining the effect of AD risk factors on brain aging in healthy middle‐aged and older women, compared to men, is critical for understanding whether there are sex differences in the pathways towards AD in cognitively intact, at risk adults. The goal of this study was to use an elastic net regression model to predict the effect of family history of AD [+FH] and the APOE‐e4 [+APOE4] genotype on brain age gap (BAG) in cognitively normal women and men.

Method

This cross‐sectional study used T1‐weighted structural MRIs from the Dallas Lifespan Brain Study (DLBS), South Asian Lifespan Dataset (SALD), Montreal Memory and Aging Lifespan Study (MMALS), and Pre‐symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer’s Disease (PREVENT‐AD) cohorts. Data were collected from multiple sites: Dallas, USA (DLBS); Chonqing, China (SALD); Montreal, Canada (MMALS and PREVENT‐AD). 1067 cognitively normal adults (18‐89 years; 697 [65%] women) were randomly split into train and test sets. In the train set: 596 unknown FH (uFH) participants (mean [SD] age = 47.39 [18.46] years, 63% women); in the test set: 251 uFH (47.50 [19.15] years, 64% women) and 220 +FH participants (61.53 [6.04] years, 72% women). BAG, was measured as the difference between Predicted Age, estimated by the elastic net model, and Chronological Age.

Result

The age prediction model applied to the test set revealed greater BAG deviations in the +FH cohort compared to the uFH cohort (31% vs. 74% of the age variance, respectively; MAE = 8.22 years). A significant interaction was observed between FH status and Sex: +FH women had more advanced brain aging compared to +FH men. APOE genotype interacted with Sex in the +FH group: +APOE4 women had more positive BAG than +APOE4 men. In a sub‐cohort of individuals with AD risk factors, we observed sex differences in the role of modifiable factors of Body Mass Index and physical activity in preserving brain aging.

Conclusion

AD risk factors have more negative consequences to brain aging in cognitively normal women with family history than men with family history, but that modifiable factors can interact with genetic factors to potentially protect against brain aging.
A global resilience score captures associations with AD pathology and predicts cognitive decline in cognitively healthy older adults
Authors: Dobyns Lindsey , Zhuang Kailin , Baker Suzanne L. , Jagust William J. , Harrison Theresa M.
Published: February 2022

Background

The concepts of resilience and reserve were developed to help explain the variability in the relationship between pathology and cognition in older adults. We created a global resilience score that considers cognitive reserve, brain reserve, and cognitive resilience. We examined the relationship between global resilience and cross‐sectional PET measures of amyloid (PiB) and tau (FTP) and longitudinal change in cognition.

Method

130 cognitively normal older adults over the age of 60 (76.13±6.13 years, 76% F, 55% PiB+) were included in the analysis. Confirmatory factor analysis was used to create composite scores for episodic memory (EM) and executive function (EF). A partial least squares path model was used to derive a global resilience factor, a second‐order latent variable, from three first‐order latent variables estimating cognitive resilience, brain reserve, and cognitive reserve (Fig 1). PET data were coregistered to the structural MRIs and extracted from FreeSurfer‐segmented regions. A global PiB DVR and partial volume corrected FTP SUVR regional values were calculated. Longitudinal change in cognition was calculated as the slope of the linear fit over time for EM and EF.

Result

There were no significant relationships between global resilience and global PiB DVR (Fig 2A). Greater global resilience score was associated with lower entorhinal (ERC) FTP SUVR across the whole sample (R2 = 0.079, p = 0.001) and in PIB‐ (R2 = 0.062, p = 0.032) and PIB+ individuals (R2 = 0.088, p = 0.029) separately (Fig 2B). In PiB+ individuals, lower global resilience scores predicted greater decline in EM (R2 = 0.144, p = 0.008) and in EF (R2 = 0.098, p = 0.030) with PiB‐ individuals showing no significant relationships (Fig 3).

Conclusion

Global resilience score is associated with ERC tau and predicts cognitive change in amyloid+ individuals for both EM and EF. Our model reflects the proposed sequence of biomarker change in AD as global resilience is unassociated with PiB DVR but significantly correlated with ERC tau and cognitive change. These results indicate that a computed global resilience variable derived from measures of cognitive reserve, brain reserve and cognitive resilience is related to AD pathology and cognitive trajectory.