bluuebunny/crossref_metadata_2025 huggingface dataset:
Concept development of self appraisal of caregiving in family caregivers of older adults with dementia: A convergent parallel mixed methods design
Authors: Karimi Zahra , Farhadi Akram , Foroughan Mahshid , Mohammadi Farahnaz , Rassouli Maryam
Published: December 2020

Background

The caregivers‟ assessment of their own caregiving is considered the most important concept in exploring their experiences and has a major role in care outcomes. This study was conducted with the aim to develop the concept of self appraisal of caregiving in family caregivers of older adults with dementia.

Method

mixed method with convergent parallel design was used to clarify and determine different dimensions of self appraisal of caregiving among caregivers of dementia patients. The study consisted of two parts: qualitative and quantitative. Confirmatory factor analysis and calculation of goodness of fit indices were performed on the data gathered from 236 family caregivers who were entered the study by convenient method to confirm the 5 factors of the revised caregiving appraisal scale ( RCAS) (caregiving burden, satisfaction, mastery, demand, and impact) in Iranian family caregivers of older adults with dementia. The data were saturated after interviews with 12 primary caregivers .Confirmatory factor analysis was performed in LISREL‐8.8 software in Windows®.

Result

In the quantitative analysis, 5 dimensions of RCAS were confirmed, which were discussed and compared with the obtained qualitative themes in the rest of the study. The content and face validities of the scale were confirmed according to the views of the family caregivers and the panel of experts. The confirmatory factor analysis results reported appropriate values for all the fit indices (RMSEA = 0.046, df / X2 = 2.428, CFI = 0.98, AGFI = 0.84 and GFI = 0.9), and the 5‐factorial model was confirmed with 27 items. The scale‐level Cronbach's alpha was reported as 0.894 and the scalelevel ICC as 0.94. Besides the confirmation of the 5 dimensions of RCAS, in the qualitative phase, other dimensions also emerged including “ caregiving burden”, “caregiving satisfaction”, ”losses and threat”, “ personal growth”, “philosophy of care” and “caregiving gains”.

Conclusion

According to the results, the Persian version of RCAS showed good validity and reliability, with 5‐factor structure that matched the original version. Therefore, I it can be an appropriate tool for assessment of caregiving and the deigned interventions to change it in family caregivers of patients with dementia.
A 48‐year‐old female, with a family history of AD PSEN1 mutation, who developed mild cognitive impairment and tried ketogenic diet‐associated medium‐chain triglyceride as treatment
Authors: de Andrade Lima Gustavo Melo , Corrado Marta , Gregório Marcela Marques de Oliveira , Bertolucci Paulo Henrique Ferreira
Published: December 2020

Background

48 years old female, biologist researchers, with a family history of AD PSEN1 mutation, symptoms compatible with Mild Cognitive Impairment (MCI) due to probable Alzheimer's disease. As part of clinical approach Ketogenic Diet and medium‐chain triglyceride was tried combined with conventional treatment.

Method

the patient had a 2 ‐year long history of amnestic symptoms with a slow worsening, when medical help was sought. She underwent neurological and neuropsychological evaluation, magnetic resonance and specific genetic tests. It was observed memory and attention deficit, executive functions impairment; left hippocampal atrophy, ApoE E2/E3 profile and a variant of uncertain significance of PSEN1. At 48, she was classified as Mild Cognitive Impairment and started a treatment with middle‐chain triglycerides and Ketogenic Diet. Before starting the treatment, she underwent another neuropsychological evaluation, PET‐FDG and cerebrospinal fluid biomarkers profile. During the treatment, she will be monitored weekly by a nutritionist expert in ketogenic diet. After three months of treatment, she will repeat tests and exams.

Result

Currently, the patient is being treated, until March 2020, at the end of it she will repeat tests and exams. According to previous studies1, 6 weeks of modified ketogenic diet, is associated with an improvement of the cerebrospinal fluid biomarker profile, cerebral perfusion, and cerebral ketone body uptake, in older adult with risk for Alzheimer Disease.

Conclusion

This case is of great importance in describing a woman’s history with the PSEN1 mutation, who underwent a Ketogenic Diet treatment while diagnosed with MCI. Regardless of the outcome, this case is essential to identify the effects of ketogenic diets on the biomarkers and neuropsychological tests on patients with the same profile. References: 1) Neth, B.J., Mintz, A., Whitlow, C., Jung, Y., Sai, K.S., Register, T.C. Kellar, D., Lockhart, S.N., Hoscheidt, S., Maldjian, J., Heslegrave, A.J., Blennow, K., Cunnane, S.C., Castellano, C.‐A., Zetterberg, H., Craft, S., Modified Ketogenic Diet Is Associated With Improved Cerebrospinal Fluid Biomarker Profile, Cerebral Perfusion, And Cerebral Ketone Body Uptake In Older Adults At‐Risk For Alzheimer’s Disease: A Pilot Study, Neurobiology of Aging (2019).
Towards a novel set of GPS‐derived metrics to identify the differences between mobility patterns of cognitively intact older adults and older adults with dementia
Authors: Bayat Sayeh , Ye Bing , Stasiulis Elaine , Rapoport Mark J , Naglie Gary , Mihailidis Alex
Published: December 2020

Background

Maintaining an active lifestyle and participating in social activities are key components of healthy ageing. These components rely on the individuals’ ability to remain mobile out of home. The global positioning system (GPS) is increasingly used to assess outdoor mobility of older adults. However, there is a gap in establishing a framework that recognizes the differences between mobility patterns of cognitively intact older adults and older adults with dementia (OAwD). We propose a set of GPS‐derived metrics to identify these differences, which can be used to evaluate changes in mobility patterns of OAwD over time.

Method

We analyzed the mobility profiles of 15 older adults from the greater Toronto area using GPS technology. Participants were aged between 65 and 90 years (M=74.9, SD=7.05) and were either cognitively healthy (n = 8) or diagnosed with dementia (n = 7). First, we created GPS‐based features representing different dimensions of outdoor mobility. These features include (1) the typical distance covered by individuals, (2) randomness of the travel patterns, (3) the spatial variation of the GPS locations, (4) the number of distinct stops visited per day, (5) the number of daily trips away from home, (6) the score of three levels of outdoor life‐space, and (7) the maximum distance travelled from home. Then, we used Recursive Feature Elimination (RFE) with Random Forest (RF) to select the most important mobility features with respect to cognitive status.

Result

A total of 55,580 GPS points were collected by the 15 unique participants over a period of 4 to 8 weeks. The RFE method indicated that features (1), (2), (3), and (5) had the strongest association with cognitive status. Our results suggested that OAwD displayed more predictability (i.e. smaller randomness) in travel patterns compared to the controls (OAwD: M=4.82, SD=0.57 vs. CTL: M=5.62, SD=0.71). Furthermore, the OAwD made fewer daily out‐of‐home trips compared to the controls (OAwD: M=1.06, SD=0.79 vs. CTL: M=1.65, SD=0.45), and covered smaller distances compared to the controls (OAwD: M=12.27, SD=11.73 km vs. CTL: M=15.78, SD=24.31 km).

Conclusion

The proposed set of GPS‐based features identified the differences between mobility patterns of cognitively intact older adults and OAwD.
A consensus proteomic analysis of Alzheimer’s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation
Authors: Johnson Erik C.B. , Dammer Eric B. , Duong Duc , Ping Lingyan , Zhou Maotian , Yin Luming , Higginbotham Lenora A. , Guajardo Andrew , White Bartholomew , Troncoso Juan C. , Thambisetty Madhav , Montine Thomas J. , Lee Eddie B. , Trojanowski John Q. , Beach Thomas G. , Reiman Eric M. , Haroutunian Vahram , Wang Minghui , Schadt Eric , Zhang Bin , Dickson Dennis W. , Ertekin‐Taner Nilufer , Golde Todd E. , Petyuk Vladislav A. , Jager Philip L. , Bennett David A. , Wingo Thomas S. , Rangaraju Srikant , Hajjar Ihab , Shulman Joshua M. , Lah James J. , Levey Allan I. , Seyfried Nicholas T.
Published: December 2020

Background

Our understanding of the biological changes in the brain associated with Alzheimer’s disease (AD) pathology and cognitive impairment remains incomplete. Unbiased discovery proteomic analysis of AD brain can help to increase our understanding of these changes.

Method

We analyzed dorsolateral prefrontal cortex, precuneus, and temporal cortex of control, asymptomatic AD, and AD brains from multiple different centers by label‐free quantitative mass spectrometry and weighted protein co‐expression analysis to obtain a consensus protein co‐expression network of AD brain. We also analyzed cerebrospinal fluid to investigate potential biomarkers related to this network.

Result

The network consisted of 13 protein co‐expression modules. Six of these modules correlated with amyloid‐β plaque burden, tau neurofibrillary tangle burden, cognitive function, and clinical functional status, and were altered in asymptomatic AD, AD, or in both disease states. These six modules reflected synaptic, mitochondrial, sugar metabolism, extracellular matrix, cytoskeletal, and RNA binding/splicing biological functions. The identified protein network modules were preserved in a community‐based cohort analyzed by a different quantitative mass spectrometry approach. They were also preserved in temporal lobe and precuneus brain regions. Some of the modules were influenced by aging, and showed changes in other neurodegenerative diseases such as frontotemporal dementia and corticobasal degeneration. The module most strongly associated with AD pathology and cognitive impairment was the sugar metabolism module. This module was enriched in AD genetic risk factors, and was also highly enriched in microglia and astrocyte protein markers associated with an anti‐inflammatory state, suggesting that the biological functions it represents may serve a protective role in AD. Proteins from the sugar metabolism module were increased in cerebrospinal fluid from asymptomatic AD and AD cases, highlighting their potential as biomarkers of the altered brain network.

Conclusion

In this study of >2000 brains and nearly 400 cerebrospinal fluid samples by quantitative proteomics, we identify proteins and biological processes in AD brain that may serve as therapeutic targets and fluid biomarkers for the disease.
Alzheimer’s disease biomarker roadmap 2020: Second‐generation tau PET tracers
Authors: Bischof Gerard N. , Dodich Alessandra , Ashton Nicholas J , Boccardi Marina , Barthel Henryk , Carrillo Maria C. , Chiotis Konstantinos , Corre Julie , Démonet Jean‐François , Gietl Anton F. , Johnson Keith A. , Hansson Oskar , Leuzy Antoine , Lorenzi Marco , Nordberg Agneta K , Ossenkoppele Rik , Rabinovici Gil D. , Ratib Osman , Sabri Osama , Treyer Valerie , Unschuld Paul G. , Villemagne Victor L.L. , Wolters Emma E. , Winblad Bengt , Frisoni Giovanni B. , Garibotto Valentina , Drzezga Alexander
Published: December 2020

Background

Selective positron emission tomography (PET) tracers to target neurofibrillary tangles of the second generation have indicated to overcome some of the methodological issues observed with the tau‐tracers of the first generation. How these second‐generation tau tracers may be better suitable for clinical practice was assessed in the context of the Geneva Biomarker Roadmap Initiative during and prior to a two‐day workshop (Geneva, November 2019).

Method

Guided by a framework for systematic validation of oncological diagnostic biomarkers adapted for the implementation of biomarker quantifying the pathological hallmarks of Alzheimer’s Disease (AD), we evaluated the performance of the tau‐selective tracers of the second generation. Subsequently we defined research priorities focusing on the advancement of the framework, with the goal for implementation of these PET tracers in clinical practice.

Result

All tracers identified as second generation, have provided evidence for in vitro binding to tau tangles in tissue samples of patients with and without Alzheimer’s disease. Additionally, in vivo pharmacokinetic modeling has been successfully achieved for some (e.g., 18F‐MK‐6240, 18F‐PI‐2620) but not all second‐generation tau tracers (e.g., GTP‐1, 18F‐JNJ‐067). Overall, observational cross‐sectional studies have provided preliminary evidence on the diminished extent of off‐target binding, high discriminatory ability between healthy and diseased populations and sensitivity in clinically diverse samples (e.g., 18F‐RO‐948, 18F‐MK‐6240, 18F‐PI‐2620).

Conclusion

A readily implementation of the tau tracer of the second‐generation in clinical practice is limited by the scarcity of comprehensive data analysis with bigger samples sizes and by the overall lack of end‐of‐life studies. However, the goal of the second‐generation tau tracers to overcome some of the methodological issues raised by the first generation tau tracers is partially achieved. Finally, the adaptation of the oncological diagnostic framework to the clinical validity of biomarkers measuring AD pathology has proven most useful in formulating new practical research goals to advance the clinical utility of the second generation tau tracer.
Proteomic, transcriptomic and functional characterization of human astrocyte‐derived extracellular vesicles upon inflammatory activation
Authors: You Yang , Borgmann Kathleen , Edara VenkataViswa , Stacy Satomi , Ghorpade Anuja , Ikezu Tsuneya
Published: December 2020

Background

Astrocytes in the central nervous system provide supportive neural functions and mediate inflammatory responses from microglia. Increasing evidence supports their critical roles in regulating brain homeostasis in response to pro‐inflammatory factors such as cytokines and pathogen/damage‐associated molecular pattern molecules in infectious and neurodegenerative diseases. However, the underlying mechanisms of the trans‐cellular communication is still unclear. Extracellular vesicles (EVs) can transfer a large diversity of molecules such as lipids, nucleic acids and proteins for cellular communications. The purpose of this study is to characterize the EVs cargo proteins derived from human primary astrocytes (AstrEVs) under both physiological and pathophysiological conditions.

Methods

We performed a quantitative proteomic and transcriptomic analysis of exosomes purified from human primary astrocytes with or without interleukin 1‐β (IL1‐β) stimulation in vitro. Exosome‐enriched fractions were purified by size‐exclusion columns. The total proteins isolated from the EVs were run on 1D SDS‐PAGE and mass spectrometry. miRNA was isolated from EVs and subjected to Affymetrix miRNA 4. 0 Array. The data are subjected to bioinformatic analysis and validation for select molecules. Human astrocyte‐derived EVs were tested for their effect on neuronal differentiation and maturation by live confocal imaging and multi‐electrode array.

Results

Label‐free quantitative proteomic profiling revealed a notable up‐regulation of proteins including actin‐associated molecules, integrins and major histocompatibility complex in IL‐1β‐AstrEVs compared to CTL‐AstrEVs, which were involved in cellular metabolism and organization, cellular communication and inflammatory response. They were also significantly associated with the increased signaling of pathogenic molecules such as APP and tau. IL‐1β‐AstrEVs show increased uptake by primary murine cortical neurons compared to CTL‐AstrEVs, which was partially suppressed by RGD peptide, a pan‐integrin inhibitor. Additionally, treatment of neurons with IL‐1β‐AstrEVs also reduced neurite outgrowth, branching and neuronal firing.

Conclusions

These findings provide insight for the molecular mechanism of the AstrEVs’ effects on neural uptake, neural differentiation and maturation, and its alteration in inflammatory conditions, which may be relevant to neuroinflammation‐mediated Alzheimer’s disease progression.
The influence of cerebrovascular disease in dementia with Lewy bodies and Parkinson’s disease dementia
Authors: Hijazi Zina , Yassi Nawaf , Watson Rosie
Published: December 2020

Background

Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), is a common form of neurodegenerative dementia. The frequency and influence of cerebrovascular disease in LBD is not well understood but may be an important contributor to symptoms and outcome.

Method

A comprehensive literature search was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) guidelines using the electronic databases Medline and Embase. Studies included assessed the presence and/or location of cerebrovascular lesions using either MRI or neuropathological examination of DLB or PDD. Specific lesions considered included white matter hyperintensities (WMH), cerebral amyloid angiopathy (CAA), cerebral microbleeds (CMB), macroscopic infarcts, microinfarcts and intracerebral haemorrhage.

Result

Of the search results (N=3923 articles), 53 were relevant, including 25 studies on WMH (DLB n=438, PDD n=532), 15 on CMB (DLB n=253 PDD n=197) and 12 examining microinfarcts (DLB n=186, PDD n=18). Most studies on WMH reported an increased severity of WMH in DLB compared to PDD, PD and healthy controls, and in PDD compared to PD using visual rating scales. In PD, WMH were associated with progression to PDD in longitudinal studies. CMB were more prevalent in DLB (17‐45%) compared to PDD and healthy controls, and in PDD compared to PD. There was an increased prevalence of microinfarcts in DLB (15‐80%) compared with controls. LBD did not appear to affect the prevalence of gross or lacunar infarcts or intracerebral haemorrhage. Some studies reported that WMH and CMB were associated with lower scores on neuropsychological testing in DLB.

Conclusion

Differing cerebrovascular lesion types and detection methods in the studies limit conclusions, with some conflicting results. There was an increased prevalence of certain cerebrovascular lesions in DLB compared to PDD, PD and controls, and in PDD compared to PD and control participants. The influence of cerebrovascular disease on the risk of LBD, disease progression and interaction with other co‐pathologies (e.g. Aβ, tau) is an important area for future research.
Comparison of peer mentoring versus peer support in a 6‐month home‐based physical activity program for inactive older adults at risk of Alzheimer’s disease: Experiences from the INDIGO trial
Authors: Cox Kay L , Ellis Kathryn A , Clare Linda , Cyarto Elizabeth V , Etherton‐Beer Christopher , Ames David , Flicker Leon , Almeida Osvaldo P , LoGiudice Dina , Liew Danny , Southam Jennifer , Lautenschlager Nicola T
Published: December 2020

Background

The INDIGO RCT compared the effects of a mentor‐supported individual goal‐setting approach versus peer‐contact only on adherence to a 6‐month home‐based physical activity (PA) program for inactive individuals aged 60‐80 years with mild cognitive impairment (MCI) or subjective cognitive decline (SCD). We report on the mentoring‐peer support experiences from INDIGO.

Method

Physically active volunteers aged 50‐85 years (n = 32) recruited from the community completed demographic, attitudes to ageing, exercise self‐efficacy and mentoring self‐efficacy (self‐rating of % confidence to mentor in a PA program) questionnaires at baseline. They were randomised to mentoring utilising a motivational interviewing style of support (intervention group), or to provide basic peer contact only (Physical Activity Liaisons, PALS). Training was provided for both arms and mentors and PALS met their peer participant during a workshop. Programs were delivered via 6 scripted telephone calls during the intervention. Some mentors/PALS repeated this support for subsequent waves. Baseline measurements were repeated after 6 and 12 months of mentoring.

Result

Seven of 32 (21.9%) withdrew after randomisation and before being assigned a participant. Twenty‐five started the intervention, 20 (80%) completed 6‐months of support and 19 (76%) completed 12 months. Mean age (± SD) (n = 25) was 65.80 (6.25) years, 15 (60%) were female. Self‐efficacy for mentoring was rated similarly between groups 93.8 (15.5)% versus 95.0 (7.9)% for mentors and PALS. Adherence to the support calls was high and similar for both groups 73.7 (30.3)% for mentors and 79.6 (29.5)% for PALS. As expected average call time was significantly higher for the mentors than for the PALS 23.4 (8.9) minutes versus 9.3 (3.6) minutes for PALS (p<0.001).There was no significant difference in mentoring self‐efficacy at 6 months but after 12 months it was significantly lower in mentors 88.7 (24.7)% than PALS 97.5 (4.6)% when adjusted for baseline mentoring self‐efficacy and attitudes to ageing (p<0.05). Participation did not result in any changes in peer volunteers own PA self‐efficacy or behaviour.

Conclusion

These findings suggest that participation for longer in a more intensive mentoring program in a PA research program may impact on mentoring self‐efficacy in age‐matched volunteers.
A framework of healthy ageing for the Torres Strait: A grassroots approach to dementia risk reduction
Authors: Quigley Rachel , Russell Sarah G , Sagigi Betty , Miller Gavin , Strivens Edward
Published: December 2020

Background

Older Aboriginal and Torres Strait Islander Australians play a crucial role in the health of their communities, holding the cultural rights and responsibilities for maintaining connections to Country, caring for extended family members, and providing leadership and support in their families and within communities. Maintaining the health of older adults is crucial not only for their quality of life but also the cohesiveness of the community they live in. Dementia is a key health priority in Indigenous communities given their increased risk of dementia compared to the general population. At present, there is a lack of evidence around what healthy ageing means in the Torres Strait or how older adults can be supported through the health care system to remain in their communities. In this paper, a study protocol will be presented for review. The aim of the study is to develop a culturally appropriate framework of Healthy Ageing for Torres Strait Communities that will include dementia risk reduction strategies to enable older persons to remain living within their communities for as long, and as healthily, as possible.

Method

This project will use Participatory Action Research to enable Torres Strait communities to identify environmental, cultural, spiritual and other priorities to achieve a fulfilling and positive approach to living well as they age. Using a Continuous Quality Improvement framework, primary health care centres will develop quality improvements based on priorities identified by the community.

Results

Primary health care centres will implement best practice screening, culturally appropriate assessments, and targeted interventions to support their people to age well and remain on country and implement dementia risk reduction strategies.

Conclusion

Results will inform a culturally appropriate framework of Healthy Ageing for Torres Strait Communities to enable older persons to remain living well at home, and on Country for as long as possible with reduced dementia risk.
Vascular and neurodegenerative imaging markers are associated with increased interstitial fluid diffusion in memory clinic patients
Authors: van der Thiel Merel M. , Freeze Whitney M. , Verheggen Inge C.M. , Wong Sau May , de Jong Joost J. , Postma Linda A. , Verhey Frans R.J. , Ramakers Inez H.G.B. , Backes Walter H. , Jansen Jacobus F.A.
Published: December 2020

Background

Diffusion measurements in brain tissue may reveal various diffusion regimes reflecting different microstructural topologies, ranging from fast blood circulation, intermediate diffusion in wider interstitial spaces, to highly restricted inter‐ and intra‐cellular diffusion. Intravoxel incoherent motion MRI can detect an intermediate diffusion component, which is thought to be a proxy of brain tissue damage. This intermediate component might be relevant for studying amyloid clearance pathways, but currently remains incompletely understood. This study aims to increase our understanding of this intermediate component by studying associations with vascular (i.e. white matter hyperintensity (WMH) volume) and neurodegenerative (i.e. hippocampal atrophy) imaging markers in a sample of memory clinic patients, who display a wide range of cognitive abilities and variation in neurovascular and neurodegenerative pathology.

Method

Forty patients (Alzheimer’s disease dementia (AD, n=15), mild cognitive impairment (n=16), vascular cognitive impairment (VCI, n=9)) and 34 healthy controls underwent a 3T MRI protocol. The intermediate diffusion component was identified with spectral analysis using non‐negative least squares (Figure 1), and the contribution of the intermediate component to the signal in each voxel was determined by quantifying its volume fraction fint. The median of fint was determined for the following regions of interest (ROIs): cortical gray matter (GM), subcortical GM, WMH and normal appearing white matter (NAWM). A multivariate linear regression model incorporating age and gender was conducted to investigate group differences. Multiple linear regression was employed to investigate the association of fint per ROI with the vascular and neurodegenerative markers, additionally adjusting for total intracranial volume.

Result

AD and VCI patients showed increased f
int in GM and NAWM relative to controls (Figure 2). The fint was found to be associated to WMH and/or hippocampal volume, dependent on the brain region (Table 1).

Conclusion

The intermediate component is associated with both vascular and degenerative markers, but this effect is region dependent. The group differences indicate a relation between fint and clinical phenotype. Brain regions where fint is affected by both vascular and degenerative markers show abnormally high fint in AD, which emphasizes the complexity to separate vascular and degenerative influences on AD pathology.
Cantonese adaptation of melodic intonation therapy (MIT) for dementia patients
Authors: Law Tammy Sheung Ting , Fung Andrea Pui Ting , Fong Manson Cheuk‐Man , Cheung Daphne Sze Ki , Wang William Shiyuan
Published: December 2020

Background

Receptive and expressive speech problems in dementia (e.g., difficulty in understanding complex concepts, incoherent speech) have been well‐documented. Melodic Intonation Therapy (MIT) is a neurologic music therapy technique that was first developed to assist speech recovery in patients with post‐stroke aphasia. While this combination of music and language has been reported to be effective for aphasics, the possible effects of an adapted MIT for the dementia population has not yet been investigated.

Methods

Nine literate, native Cantonese‐speaking participants with dementia (mean age = 80 ± 7.09 years, 3 male, mean MMSE = 16.89 ± 3.69) and with reported expressive speech problems by caregivers were recruited from an elderly day care centre of the Hong Kong Alzheimer’s Disease Association. Participants completed a 3‐week group‐based MIT program (30 minutes per session, twice a week) designed to improve the speech functions of dementia patients. Over the whole program, two children songs with melody familiar to elderly but newly rewritten lyrics were taught and practiced. The subtests of spontaneous speech and auditory comprehension in Cantonese Aphasia Battery were conducted pre‐ and post‐intervention to assess the changes in expressive and receptive speech of participants.

Results

Rates of consent and retention were both 100%, with an attendance rate of 89%. Pre‐post analyses using Wilcoxon signed rank test showed significant improvement in the sub aphasia quotient of spontaneous speech after intervention (Z = 2.54, p < .05). Further analyses revealed that this improvement was contributed solely from the fluency score (Z = 2.69, p < .01), but not from information (Z = ‐0.27, p > .78). Only a trend of improvement was observed for the sub AQ of auditory comprehension (Z = 1.68, p = .093). Qualitative analyses suggested possible improvements in different language domains (e.g., specificity of item description, syntactic complexity of sentence structure).

Conclusion

This study is the first to evaluate the feasibility and preliminary effects of the Cantonese adaptation of MIT for dementia. Our results demonstrated positive effects in the fluency of spontaneous speech (significant) and auditory comprehension (trending), showing the potentials of this music therapy in enhancing speech performance of dementia patients.
Adaptation of an evidence‐based intervention for family carers of people living with dementia for delivery to UK‐based South Asian carers: Widening access to START (Strategies for Relatives)
Authors: Sommerlad Andrew , Amador Sarah , Mukadam Naaheed , Rapaport Penny , Lang Iain A , Livingston Gill
Published: December 2020

Background

Family members caring for a relative with dementia often become anxious or depressed. We developed START (STrAtegies for RelaTives) for family carers of relatives with dementia to promote helpful coping strategies. START is the first clinically‐ and cost‐effective intervention of its kind, and is currently delivered within UK National Health Service. However, barriers to delivery of START to South Asian carers include delayed presentation to health services, stigma, and language. In this study, we therefore aimed to widen access to START by adapting it for delivery to UK‐based South Asian family carers.

Methods

In Phase 1, we used the Cultural Treatment Adaptation Framework (CTAF) to guide data collection, through a semi‐structured interview guide. We interviewed 15 UK‐based South Asian carers about START and factors affecting its implementation to inform modifications. We transcribed interviews and researchers double‐coded them independently, using the CTAF to organise the findings.

In Phase 2, we trained and supervised facilitators to deliver the adapted START intervention to South Asian family carers. In Phase 3, after START delivery, we used the i‐PARIHS framework to evaluate the implementation, through qualitative and quantitative interviews with all carers and qualitative interviews with facilitators.

Results

We interviewed 15 South Asian carers in London and Bradford, UK. There were no changes to START’s core components. We incorporated cultural values and beliefs into the START intervention manual by modifying and adding in new examples and testimonials, and adding prompts. We also translated the manual into Urdu, a common South Asian language in the UK, and produced an audio version of the manual in Urdu. The project group met to agree on the modifications. The intervention was delivered to 13 family carers between January 2019 and January 2020 including 4 in Urdu and conducted interviews afterwards assessing satisfaction with the intervention and its effect on depression and quality of life.

Conclusions

We used multiple methodologies to identify barriers and facilitators to effective delivery of a psychosocial intervention for South Asian family carers based in the UK. We found that adaptations to the content and delivery of an intervention may improve its acceptability and efficacy.
A multicenter, randomized controlled feasibility trial for the programs of the SoUth Korea study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at‐risk elderly people (SUPERBRAIN)
Authors: Choi Seong Hye , Jeong Jee Hyang , Moon So Young , Hong Chang Hyung , Na Hae Ri , Park Yoo Kyoung , Park Hee Kyung , Song Hong Sun , Lee Sun Min , Choi Muncheong , Park Kyung‐Won , Kim Byeong C , Cho Soo Hyun , Chun Buong‐O
Published: December 2020

Background

Multidomain interventions can be useful for the prevention of dementia. We have developed the programs of SoUth Korea study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at‐risk elderly people (SUPERBRAIN), which consists of a facility‐based (FMI) and a home‐based multidomain intervention (HMI) program suitable for elderly Koreans. This study aims to investigate the feasibility of the SUPERBRAIN programs before a large‐scale randomized controlled trial (RCT).

Method

We recruited 152 participants from eight centers, among those without dementia aged 60‐79 years with at least one modifiable dementia risk factor. They were randomly assigned: 51 to the FMI arm, 51 to the HMI arm, and 50 to the control arm. The 6‐month multidomain intervention consisted of: management of metabolic and vascular risk factors, cognitive training and social activity, physical exercise, nutritional guidance, and motivational enhancement programs. The intervention program is determined feasible if the following success criteria are met: 1) a minimum retention rate of 75% at week 24; 2) a minimum adherence to the intervention program of 75%; and 3) at least no difference from the control arm in the change of the total scale index score of the Repeatable Battery for the Assessment of Neuropsychological Status from baseline to study end. Main secondary outcomes are disability, depressive symptoms, quality of life, vascular risk factors, physical performance, nutritional assessment, and motivation questionnaire.

Result

Screening began in May 2019 and was completed in August 2019. The intervention is ongoing as planned. There were no significant differences in the bassline age (71.7 ± 4.8 vs. 70.9 ± 4.9 vs. 70.7 ± 4.8 years, p = 0.57) and level of education (10.2 ± 4.8 vs. 9.9 ± 5.2 vs. 10.5 ± 4.8 years, p = 0.82) among the FMI, HMI, and control arms. The proportion of women did not differ in FMI, HMI and control arms (72.5% vs. 72.5% vs.78.0%, p = 0.77). The study will be completed in March 2020.

Conclusion

This study will inform the applicability of these multidomain intervention programs in at‐risk elderly people and contribute to the success of a subsequent RCT.
Chronicity of amyloid: Methods for estimating amyloid onset and clinical research applications
Authors: Betthauser Tobey J. , Koscik Rebecca L. , Jonaitis Erin M. , Cody Karly Alex , Vasiljevic Eva , Erickson Claire M. , Mueller Kimberly D. , Clark Lindsay R. , Engelman Corinne D. , Stone Charles K. , Christian Bradley T. , Asthana Sanjay , Johnson Sterling C.
Published: December 2020

Background

Prior works including our recent publication suggest amyloid PET levels provides information about the duration of amyloidosis exposure. This study compares two methods for modeling longitudinal amyloid trajectories and estimating the onset age of amyloid positivity (A+). Methods are applied to investigate similarities and differences across Apolipoprotein E (APOE) genotypes.

Methods

Two modeling strategies (iterative local linear approximation, ILLA; group‐based trajectory modeling, GBTM) were applied to [C‐11]PiB PET data acquired from the Wisconsin Alzheimer’s Disease Research Center and the Wisconsin Registry for Alzheimer’s Prevention (N=272). Amyloid burden was ascertained for each PiB scan by calculating a global mean distribution volume ratio (DVR). Annualized DVR rate vs. DVR was characterized in a subset with longitudinal data (n=179 from WRAP, baseline age mean±SD=61.0±6.2 years, 6.2±2.1 years follow‐up). This subset was used to train ILLA and GBTM models. Model performance was evaluated by aligning each person’s last scan to the modeled curve and calculating the explained variance in antecedent scans. Estimates of A+ age (EOA+) were compared across methods for APOE genotypes in all participants with high accumulation probabilities.

Results

ΔDVR/yr was homogeneous for given levels of amyloid. Longitudinal DVR slopes were mostly constant and all were positive for DVR>1.2. ILLA and GBTM methods performed similarly with ILLA explaining slightly more variance in previous scans and having a shorter timeline compared to GBTM (Figure 1). EOA+ were similar across methods within APOE genotypes (ILLA 2.7±1.9 years >GBTM). Relative to APOE‐e3e3 carriers, e3e4 and e4e4 carriers had EOA+ 2.2 and 5.4 years earlier (Table 1). Accumulation rates were similar in APOE‐e4 carriers and non‐carriers (Figure 2).

Conclusions

These results suggest the chronic process of amyloid accumulation is remarkably similar between individuals. This homogeneity is amenable to modeling approaches that estimate age of A+ and thereby the duration of A+ exposure reflecting the chronicity of amyloidosis. Applying these concepts to APOE data indicated e4 carriers accumulate amyloid earlier rather than faster. These findings highlight how the combination of amyloid chronicity and A+ age concepts enable new lines of discovery related to AD risk and resilience. Future work will apply these methods to other cohorts.
Predictors of behavioral and psychological symptoms and caregiver burden in spousal caregivers of people with dementia: A longitudinal study
Authors: Lawlor Brian , Pertl Maria , Brennan Sabina , Robertson Ian H
Published: December 2020

Background

As the number of people with dementia and the demands on family caregivers continues to increase, it is important to understand the factors associated with increased burden in order to identify effective interventions that reduce burden and improve the quality of life for both the caregiver and the care‐recipient (C‐R).

Method

We examined the predictors of behavioral and psychological symptoms of dementia (BPSD) and caregiver burden in 253 spousal caregivers of people with dementia (mean age 69.64 +7.84; 64.8% female; mean length of caring 59.44 +39.29 months) followed up over 12 months.

Result

45% of spousal caregivers were experiencing moderate to severe burden levels at baseline as measured by the Zarit Burden Index. One‐year follow up data was available on 205 caregivers: 151 were still caring at home; 34 C‐Rs were in long‐term care; 20 C‐Rs were deceased. Among those who were still caring at home at follow‐up, caregiver depression, loneliness, anxiety and self‐efficacy for symptom management at baseline predicted BPSD severity at follow‐up, controlling for baseline BPSD severity, number of years providing care, the number of caregiving hours per day, and functional impairment. Baseline depression, loneliness, anxiety, self‐efficacy and BPSD severity also predicted caregiver burden at follow‐up. However, only BPSD severity predicted burden at follow‐up in a combined model, controlling for burden, number of years providing care, the number of caregiving hours per day, and functional impairment at baseline.

Conclusion

While the strongest predictor of caregiver burden is the severity of BPSD, the emotional health of caregivers may also contribute to greater BPSD severity over time. Targeting BPSD directly while at the same time addressing caregiver factors, such as depression, anxiety, loneliness and self‐efficacy for symptom management, has the potential to impact on the severity of BPSD and improve the quality of life of spousal carers of people with dementia.
Defining agitation, apathy and other psychiatric symptoms in cognitive impairment and dementia: Why we need to intervene
Authors: Sano Mary ,   International Psychogeriatric Association
Published: December 2020

Background

International Psychiatric Association (IPA) has a long history of defining and treating the behavioral and psychiatric symptoms that occur with cognitive impairment and dementia, including agitation and apathy. This presentation will describe the international and collaborative approach to creating definitions and diagnoses. Also a description of how these efforts have fostered trial design and can direct development of protocols with evidence‐ based selection of populations and meaningful outcomes.

Method

The methodology used by the IPA and other associations to characterize behavioral symptoms in aging and dementia begins with a review of the extant literature and the creation of a survey around the key elements of the diagnosis or definition of a given condition such as agitation or apathy. Elements of the definition are selected from the field and the surveys are disseminated via a link in an email. The email is distributed widely, to member of IPA and to its more than 20 different affiliates, which represent national organizations in geriatric psychiatry and allied fields. International working groups use the responses to formulate criteria that have meaning and importance to the largest number of stakeholders including, providers, regulators, researchers and patient advocates. The uptake of the criteria and their success in defining treatable conditions is monitored and in interactive process of updating the definitions to improve clinical utility is promoted.

Result

This approach has been used to create guidelines for defining agitation, apathy and psychosis. The presentation will include a review of the results of this process for agitation in which the publication of the provisional guidelines were followed by a notable increase in clinical trials and other research to address interventions and in work to improve outcome measures. Recent work in apathy has also provided support for selecting clinically relevant outcomes including measures of function, cognition and caregiver burden.

Conclusion

International collaboration to define psychiatric and behavioral symptoms associated with cognitive impairment can provide the stimulus to developing meaningful interventions.
The prognostic role of microglia and tau PET in Alzheimer’s disease
Authors: Malpetti Maura , Kievit Rogier A , Passamonti Luca , Jones P Simon , Tsvetanov Kamen A , Rittman Timothy , Mak Elijah , Nicastro Nicolas , Bevan‐Jones W Richard , Su Li , Hong Young T , Fryer Tim D , Aigbirho Franklin I , O'Brien John T , Rowe James B
Published: December 2020

Background

Neuroinflammation is part of the pathophysiology of Alzheimer’s disease (AD), in addition to amyloid‐β plaques and tau neurofibrillary tangles. PET markers of microglial activation have indicated inflammation of temporo‐parietal regions, in proportion to disease severity. Here we test the prognostic value of [11C]PK11195 PET on longitudinal clinical decline in AD, alone and in combination with MRI and tau ([18F]AV‐1451) PET imaging.

Method

Twenty‐six patients with Alzheimer’s dementia or amyloid‐positive Mild Cognitive Impairment, and 29 controls underwent multi‐modal assessment with [11C]PK11195 PET, [18F]AV‐1451 PET, structural MRI, and annual cognitively assessment with the Revised Addenbrooke's Cognitive Examination. Regional PET binding potentials and grey‐matter volumes from fifteen bilateral temporo‐parietal region were summarised by method‐specific Principal Component Analyses (PCAs). The rate of longitudinal cognitive decline was estimated using a Latent Growth Curve Model. The predictive value of PET and MRI on cognitive decline was tested with modality‐specific regression models, and a multi‐modality regression model.

Result

PCA on each PET ligand consistently identified one component in anterior temporal regions, and another in posterior temporo‐parietal regions, while for MRI, a single component was identified across all regions. Worse annual rate of cognitive decline correlated with higher [11C]PK11195 in the anterior temporal component (r = −0.47, p = 0.002), and in posterior temporo‐parietal regions (r = −0.39, p = 0.012). An optimal multi‐modality model was identified by stepwise regression and Bayesian selection, that included the anterior [11C]PK11195 component and both [18F]AV‐1451 components as predictors of cognitive decline (R2 = 0.418; p = 0.001), but not their interaction and not the baseline MRI.

Conclusion

These results suggest that in addition to tau pathology, microglial activation in the anterior temporal lobe plays a key role in predicting future cognitive decline in patients with AD. The results support therapeutic strategies targeting tau and microglial activation as disease‐modifying therapy against AD.
The impact of a nutritional intervention in prodromal Alzheimer’s disease: The LipiDiDiet clinical trial
Authors: Hartmann Tobias , Solomon Alina , Visser Pieter Jelle , Hendrix Suzanne B , Blennow Kaj , Kivipelto Miia , Soininen Hilkka ,   LipiDiDiet Clinical Study Group
Published: December 2020

Background

Diet and nutrition are important modifiable risk factors for Alzheimer’s disease (AD). For the last two decades, the LipiDiDiet consortium has been investigating the role of nutrients and their synergistic action on key AD pathological features. Based on preclinical results, 11 nutrients were selected which, when applied in this specific combination, gave the best results in rodent AD models: i.e. the omega‐3 fatty acids DHA and EPA, phospholipids, vitamins B6, B12, folic acid, C and E, choline, selenium, and UMP. The LipiDiDiet trial1 is a 6‐year, double‐blind, parallel‐group, multi‐centre, randomised controlled clinical trial, designed to investigate effects of the specific multinutrient combination Fortasyn Connect on cognition and related measures in prodromal AD. Initial 24 month results showed significant benefit on clinical dementia rating‐sum of boxes (CDR‐SB) and hippocampal and ventricular volumes in the modified intention‐to‐treat population. Here we report previously specified primary and secondary outcomes over 36 months of intervention.

Method

Prodromal AD participants (n=311) were randomised to receive either active product (125 mL drink containing Fortasyn Connect) or a calorie‐matched placebo control once daily.

Result

162 participants completed the 36‐month period. With increasing treatment duration, the benefit of the active group over the control group exceeded what had been observed for the first 24 months (Soininen et al., Lancet Neurology 2017). For the 5‐item neuropsychological test battery (NTB) on cognition, a significant between‐group difference was observed in estimated mean change from baseline over 36 months favouring active intervention (0.212 [95% CI 0.044 to 0.380]; p=0.014; 60% reduction in decline). In addition, significant benefits were found on CDR‐SB, NTB memory, and hippocampal, ventricular, and whole brain volumes on MRI. Self‐reported compliance to the study product was high and there was no indication of safety concern.

Conclusion

We observed significantly slower decline in cognition including memory, CDR‐SB measuring cognition and function, and brain structural measures. Importantly, prolonged intervention with this specific combination of nutrients resulted in a broader range of endpoints showing statistically significant differences. Sustainable benefits lasting for 3 or more years have not been reported before in prodromal AD. Dutch Trial Register: NTR1705. 1EUFP7 N°211696 LipiDiDiet.