bluuebunny/crossref_metadata_2025 huggingface dataset:
Voxel‐based correlation of 18F‐THK5351 accumulation with gray matter structural networks in cognitively normal older adults
Authors: Shigemoto Yoko , Sone Daichi , Maikusa Norihide , Kimura Yukio , Suzuki Fumio , Fujii Hiroyuki , Sato Noriko , Matsuda Hiroshi
Published: February 2022

Background

Although gray matter (GM) structural networks based on intracortical similarities have been proposed, no studies have yet examined the correlations between GM network measures and tau. Here, we investigated the voxel‐wise correlations of GM network measures and 18F‐THK5351 accumulation in cognitively normal (CN) older adults.

Method

We recruited 47 amyloid‐negative CN older adults (65.0 ± 7.9 y age, 26 female, 14.3 ± 2.4 y education, Mini‐Mental State Examination score 29.3 ± 1.1, Wechsler Memory Scale‐Revised Logical Memory II score 13.4 ± 2.9). All participants underwent 3D T1‐weighted MRI, 11C‐PiB and 18F‐THK5351 PET scans. Single‐subject GM networks extracted from T1‐weighted MRI data based on intracortical similarities were analyzed using the graph theoretical approach. Correlations between four local network measures (betweenness centrality, clustering coefficient, characteristic path length, and degree) and 18F‐THK5351 standardized uptake value ratio (SUVR) images were evaluated at a voxel level using biological parametric mapping (BPM) toolbox in SPM. The results with the following criteria were deemed significant: a height threshold of p < .05 (family‐wise error corrected) with an extent threshold of 100 voxels.

Result

Significant positive correlations between four local network measures and 18F‐THK5351 SUVR images were detected in the bilateral caudate.

Conclusion

Using voxel‐based analysis, we detected significant positive correlations between local network measures and 18F‐THK5351 accumulation in the bilateral caudate in CN older adults. Our findings suggest that tau and neuroinflammation in CN elderly may influence local GM network in the caudate.
Features of the provision of inpatient medical care to patients with Alzheimer's disease during the SARS‐COVID‐19 pandemic
Authors: Sushko Viacheslav Viktorovich , Sushko Viktor Vasilievich
Published: February 2022

Background

With Alzheimer's disease, the patient is not only unable to help himself, but he cannot even ask for such help. This is especially dangerous for a patient during the SARS‐COVID‐19 pandemic. Since the deadly complications of SARS‐COVID‐19 are observed in the age group in which Alzheimer's disease manifests itself.

Method

We observed 26 women aged 71‐84 with Alzheimer's disease. All patients received treatment according to Alzheimer's disease treatment standards. Both amyloid‐beta and tau were found in their cerebrospinal fluid. They also showed neurodegeneration in the areas classic for Alzheimer's disease on MRI of the brain.

During a pandemic, sickness departments must wear masks and change them every 4 hours to prevent SARS‐COVID‐19 disease. In patients with Alzheimer's disease, the fulfillment of these requirements on their own is impracticable, since they have memory disorders for current events, changes in mood (apathy). Therefore, constant monitoring of medical personnel for compliance with these requirements is required.

These patients in all inpatient care periods were given masks with a built‐in 4‐hour timer and a sensor that responded to opening contacts when the mask was removed. The end of 4 hours of wearing the mask and the removal of the mask as indicated by sound and light alarms installed in the mask.

Result

This greatly facilitated the monitoring of compliance with quarantine SARS‐COVID‐19 measures in patients with Alzheimer's disease. Also, the timely change of the mask was the prevention of hypoxia that develops as a result of wetting the mask with prolonged wearing.

Conclusion

Prevention of hypoxia with the prolonged wearing of a wet mask alleviates the symptoms of Alzheimer's disease, allows the patient to convey their thoughts and feelings, and significantly improves the quality of life of patients.
The role of corpus callosum sub‐regional volume and its association to interhemispheric functional connectivity in Alzheimer’s disease (AD) and amyloid mild cognitive impairment (amyMCI)
Authors: Cheung Eva YW , Shea Yat Fung , Chiu Patrick Ka‐Chun , Kwan Joseph SK , Mak Henry
Published: February 2022

Background

Previous studies demonstrated that when compare to healthy control (HC), patients with AD and amnesic mild cognitive impairment suffered degeneration in corpus callosum (CC) [2], [3]. The volume of CC and its sub‐regions associate with cognitive impairment in AD and MCI[3].

Method

52 participants (25 healthy controls HC, 16 AD, 11 amyloid MCI), were recruited to undergo structural MRI and Resting state functional MRI (rs‐fMRI) scanning. Data Acquisition T1W Images MRI images were acquired using a Phillips Achieva 3T equipped with 32‐channel phased‐array head coil (Department of Diagnostic Radiology, the University of Hong Kong). A T1W MPRAGE and rs‐fMRI images were obtained. Voxel Mirrored Homotopic Connectivity (VMHC) was calculated based on the method used by Kelly et al 2011 [4] and Zuo et al 2010 [5]. Two‐sample T‐tests were done between diseased groups with HC and VMHC map were created using DPARSF v4.0. CC was segmented and its subregional volume were calculated by Freesurfer (v. 7.1), and were compared using ANCOVA analysis, with age, gender and total intracranial volume as covariates. Association between regional IFC and CC sub‐regional volume were calculated based on the Spearman’s correlation test, with same covariates, using SPSS (v.25.0).

Result

CC subregional volume were compared among AD, amyloid MCI and HC groups. There was no significant different in CC volume for AD group. For amyMCI group, the mid‐anterior CC (480.9mm3) was significantly larger than that of the AD (399mm3, p<0.001) and HC (419.8mm3, p <0.05)) group respectively. Also, the whole CC volume of amyMCI (3176.4mm3) was significantly larger than that of HC (2933.8mm3, p<0.05).

In correlation analysis between subregional CC volume and regional IFC, the amyMCI group demonstrated significant positive correlation between ant‐CC volume and IFC at inferior frontal operculum gyrus (r=0.827, p=0.022) and inferior frontal triangular gyrus (r=0.844, p=0.017). Positive correlation between Mid‐ant CC volume and IFC at rolandic operculum (r=0.764, p=0.046).

Conclusion

The findings demonstrated that anterior and mid‐ant CC volumes and regional IFC are positively correlated. We speculate that CC subregional volume increase promotes the regional IFC to compensate for cognitive deterioration due to amyloid deposition.
The effects of intracranial stenosis on cerebral perfusion and cognitive performance
Authors: Hilal Saima , Mutsaerts Henri J.M.M. , Ferro Doeschka A. , Petr Jan , Kuijf Hugo J. , Biessels Geert Jan , Chen Christopher
Published: February 2022

Background

Intracranial stenosis (ICS) may contribute to cognitive dysfunction by decreased cerebral blood flow (CBF) which can be measured quantitatively by Arterial Spin Labelling (ASL). Interpretation of CBF measurements with ASL, however, becomes difficult in patients with vascular disease due to prolonged arterial transit time (ATT). Recently, spatial coefficient of variation (sCoV) of ASL signal has been proposed that approximates ATT and utilized as a proxy marker for assessment of hemodynamic status of cerebral circulation. We investigate the association of ICS with CBF and sCoV parameters and its eventual effects on cognition in a memory clinic population.

Method

We included 381 patients (mean age = 72.3 ± 7.9 years, women = 53.7%) who underwent 3T MRI and detailed neuropsychological assessment. ICS was defined as ≥ 50% stenosis in any intracranial vessel on 3D Time‐of‐Flight MR Angiography. Gray matter sCoV and CBF were obtained from 2D EPI pseudo‐continuous ASL images. We used regression models to determine the effects of ICS on CBF and sCoV and eventually on cognition. Mediation analysis was further constructed to determine whether perfusion is the key link between ICS and cognitive performance. All analyses were adjusted for age, sex, hypertension, hyperlipidemia and diabetes.

Result

ICS was present in 58 (15.2%) patients. Patients with ICS had higher gray matter sCoV and lower CBF. The association with sCoV remained statistically significant after correction for cardiovascular risk factors. Moreover, ICS was associated with worse performance on visuoconstruction, which attenuated with higher sCoV. Mediation analysis showed that there was an indirect effect of ICS on visuoconstruction via sCoV.

Conclusion

These findings suggest that compromised CBF as detected by higher sCoV is related to cognitive impairment among individuals diagnosed with ICS. We also showed that sCoV partially mediates the link between ICS and cognition. Therefore, sCoV may provide valuable hemodynamic information in patients with vascular disease.
Diagnostic performance of automated MRI volumetry by icobrain DM for Alzheimer's disease in a clinical setting: A REMEMBER study
Authors: Wittens Mandy M.J. , Sima Diana M. , Houbrechts Ruben , Ribbens Annemie , Niemantsverdriet Ellis , Fransen Erik , Bastin Christine , Benoit Florence , Bergmans Bruno , Bier Jean‐Christophe , Deyn Peter Paul , Deryck Olivier , Hanseeuw Bernard J. , Ivanoiu Adrian , Lemper Jean‐Claude , Mormont Eric , Picard Gaëtane , Salmon Eric , Segers Kurt , Sieben Anne , Smeets Dirk , Struyfs Hanne , Thiery Evert , Tournoy Jos , Triau Eric , Vanbinst Anne‐Marie , Versijpt Jan , Bjerke Maria , Engelborghs Sebastiaan
Published: February 2022

Background

Magnetic resonance imaging (MRI) has become important in the diagnostic work‐up of neurodegenerative diseases. icobrain dm, a CE‐labeled and FDA‐cleared automatic tool for brain volumetry using clinical MRI scans, has shown great potential in differentiating cognitively healthy controls (HC) from Alzheimer’s disease (AD) dementia (ADD) patients in selected research cohorts (Struyfs H, et al. (2020)).This study examined the diagnostic value of icobrain dm for AD in routine clinical practice, and compared it to FreeSurfer, one of the standard tools in neuroimaging research.

Method

The Belgian Dementia Council (BeDeCo) initiated a retrospective, multi‐center Belgian study (REMEMBER). Through automated volumetric analyses of whole brain, gray matter, cortical gray matter, frontal, parietal, occipital and temporal cortices, hippocampal volumes and lateral ventricles on real‐world clinical brain MRI T1w (n=820) images across the AD continuum, icobrain dm’s (v.4.4.0) ability to differentiate diagnostic groups in the AD continuum vs. HC was compared to FreeSurfer (v.6.0). Using icobrain dm’s automated volumetric output, we also investigated which combined brain volumes contributed most to establish an AD diagnosis and could differentiate between different stages of the disease.

Result

The final study population consisted of subjects from eight Belgian memory clinics, with HC (n=89), subjective cognitive decline (SCD, n=89), mild cognitive impairment (MCI, n=350), and ADD (n=250) (Table 1). icobrain dm outperformed FreeSurfer in processing time (15‐30 minutes vs. 9‐32 hours), robustness (0 failures vs. 67 failures due to complete abortion of analysis during topology corrections) and diagnostic performance (AUC, sensitivity and specificity) in univariate differentiation between HC and ADD patients (Figure 1, Table 2). Stepwise backward regression models showed improved diagnostic accuracy for pairwise group differentiations when combining multiple brain volumes computed by icobrain dm, with highest performance obtained for distinguishing HC from ADD patients (AUC=0.914; Specificity 83.0%; Sensitivity 86.3%) (Table 3).

Conclusion

Automated volumetry has a diagnostic value for ADD diagnosis in routine clinical practice. Our findings indicate that icobrain dm’s automated volumetry can improve diagnostic certainty in a real‐world clinical setting with a significantly reduced processing time, robustness and diagnostic performance, as compared to FreeSurfer.
A scoping review of interventions tailored to the unique needs of care partners of persons with frontotemporal degeneration
Authors: Tran Leslie , Tarter Robin R , Lindauer Allison
Published: February 2022

Background

Care partners for family members with Frontotemporal Degeneration (FTD) face challenges that are complex and distinct from those faced by care partners persons with Alzheimer’s disease and related dementias (ADRD). However, while there are numerous studies addressing the negative impact of providing care to persons with ADRD, less attention is paid to the needs of care partners of persons with FTD. Understanding how interventions can be tailored to address the behavioral symptoms of FTD can inform future approaches to meeting the needs of FTD care partners.

Method

A scoping review was undertaken following Arksey and O’Malley’s systematic methodological framework. Articles were identified through a comprehensive search of PubMed, PsychINFO, and CINAHL. Peer‐reviewed, data‐based articles reporting results of interventions specifically designed to address the unique needs of care partners of persons with FTD were included in our sample. Reviews, scale development, and studies including ADRD care partners of were excluded.

Result

We identified 290 unique records and retained 42 for full text screening. One paper was added after manual search of reference lists, resulting in eight papers describing five unique interventions meeting inclusion criteria. All included studies had small sample sizes (total n ranged from 2‐30); three were randomized controlled trials. The studies were based in the US, Australia, Germany, Canada and The Netherlands, and the majority of participants were white, female spouses. Three interventions were group‐based, and two were one‐to‐one. Duration ranged from five weeks to six months. Lack of informal support, stigma, financial concerns, and coping with FTD‐associated behavioral symptoms such as apathy and disinhibition were especially salient topics for participants. Participants benefited from peer support, problem‐solving, and positive reframing activities. Statistically significant improvement in burden were reported in three of the eight papers.

Conclusion

All of the included papers suggested positive qualitative and quantitative results from the interventions, but the samples were small and homogenous. This review highlights an important gap in the science addressing the behavioral challenges FTD care partners face. These findings support the need for larger studies with more diverse populations to identify effective interventions to support families living with FTD.
Comparison of cognitive intervention delivery formats for patients with dementia—A systematic review and Bayesian network meta‐analysis
Authors: Sun Yue , Wang Zhiwen
Published: February 2022

Background

Cognitive intervention has been shown to be effective to delay cognitive decline in older adults with dementia. However, whether cognitive intervention could be effectively delivered in individual, group, telephone, guided self‐help and unguided self‐help formats remains unclear. This study aims to compare and rank the efficacy of five cognitive intervention delivery formats for older adults with dementia in improving their cognitive function.

Method

Pubmed, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), CINAHL, the Cochrane Central Register of Controlled Trials, Web of science, China National Knowledge Infrastructure database, Chinese Biomedical Literature database and Wan Fang database were systematically searched. Randomized controlled trials (RCTs) that compared the differences between different cognitive intervention delivery formats or any one of the five delivery formats with a control group in treating older adults with dementia were identified and included. The Cochrane Risk of Bias tool was used for critical appraisal. Pairwise meta‐analysis was conducted to directly examine the efficacy of each cognitive intervention formats. Network meta‐analysis (NMA) was conducted to evaluate the relative effects and rank probability of different cognitive intervention delivery formats.

Result

Totally 51 studies were included which enrolled 3388 participants. Compared with the control group, the mean difference (MD) of guided self‐help [MD = 2.48, confidence interval [CI]: (1.45, 3.53), group (MD =1.21, CI: 0.14, 2.28), individual (MD = 1.63, CI: 0.86, 2.4) could significantly improve cognitive function measured by Mini‐Mental State Examination (MMSE), while telephone (MD =2.89, CI: ‐1.41, 7.15) and unguided self‐help (MD = 2.06, CI: ‐0.29, 4.41) were not significantly inferior to control condition. Guided self‐help had the highest probability of being the best treatment among the five cognitive intervention delivery formats [the surface under the cumulative ranking curve (SUCRA= 85.13%)], followed by individual (SUCRA = 78.14%) and group (SUCRA = 77.68%).

Conclusion

For older adults with dementia, guided self‐help, group and individual cognitive intervention delivery formats appeared to be effective in improving the cognitive function. Health‐care professionals should apply personalized cognitive intervention format based on individual condition and preferences.
The feasibility and acceptability of a pilot comprehensive resilience‐building psychosocial intervention (CREST) for people with memory problems/dementia in the community
Authors: O'Sullivan Grace , Doyle Priscilla , Gallagher Niamh , Smyth Siobhán , Casey Dympna
Published: February 2022

Background

A dementia diagnosis can lead to a decline in cognitive, social, and physical health, but people with dementia can live meaningful lives and participate actively in society with psychosocial support [1‐3]. This pilot study explored the feasibility and acceptability of a comprehensive resilience‐building psychosocial intervention (CREST) for people with memory problems/dementia (PWMPD), their caregivers, GPs, and the public.

Method

Nine PWMPD and their primary caregivers living in the community (N=9 pairs) completed the CREST intervention. The three components (cognitive stimulation therapy [CST], physical exercise, and dementia education) were delivered in five programmes. The PWMPD attended a 7‐week CST programme and an 8‐week exercise programme. The caregivers attended a 6‐week educational programme. Dementia education programmes were held for the community and local GPs. Quantitative secondary outcomes for participants were assessed at baseline and following the 15‐week intervention; qualitative interviews were conducted during and post‐intervention. All study components were assessed to determine the feasibility of conducting a future definitive trial.

Result

High attendance and adherence to content were maintained for each component. The PWMPD and caregivers enjoyed each component of the CREST intervention, with only minor changes being recommended. The PWMPD enjoyed the CST and Exercise components; they felt their concentration and fitness had improved over the 15‐week intervention and particularly enjoyed the social aspects (e.g., group classes, exercising with partners from the community). Secondary elements of the Exercise component (home diaries and Fitbit use) were not feasible. Caregivers felt that they had better knowledge and understanding following their education component and reported that the social aspects (interacting and sharing experiences with each other) were important elements. The quantitative measures were confirmed feasible by participant feedback and data analysis, and health economic tools were confirmed feasible by preliminary health economic analysis. Recruitment posed significant delays to the onset and conduct of the CREST intervention.

Conclusion

The CREST intervention was acceptable to the participants and each component was considered feasible. However, significant difficulties with recruitment impacted the viability of delivering the intervention in the community and further work is needed identify barriers to the recruitment of PWMPD before a full‐scale or RCT can be conducted.
Chronic loneliness‐by‐epigenetic age effects on dementia risk in late adulthood
Authors: Lynch Morgan E , Beam Christopher R
Published: February 2022

Background

Over the last 10 years, numerous studies have been published reporting a small but significant correlation between loneliness and dementia risk. To date, few studies have tested mechanisms that mediate the longitudinal association between loneliness and dementia. DNA methylation may be one variable that explains this association, as when combined with other biomarkers, quantifies whether people’s biological age is more (or less) advanced than their chronological age. The purpose of this study is to test whether epigenetic age moderates the longitudinal trajectory of loneliness on dementia risk.

Method

The sample was drawn from the three waves of the Health and Retirement Study (n = 268, mean age = 69) collected four years apart from 2008‐2016. Loneliness scores were composed using with 11 items of the UCLA Loneliness Questionnaire. Dementia risk was quantified according to Langa‐Weir’s approach that uses the modified Telephone Interview for Cognitive Status. Epigenetic age is quantified by DNAm PhenoAge (Levine et al., 2015.). Ordinary least squares regression was used to test the interaction effect of DNAm PhenoAge and loneliness on dementia risk.

Result

A significant interaction effect between DNAmPhenoAge and longitudinal loneliness on dementia risk was found (F(7,268) = 6.98 , p < 0.001; adjusted R2 =.13). Effects of DNAm PhenoAge were greater in those with higher levels of loneliness over time, suggesting that effects of loneliness on dementia risk depend on epigenetic age.

Conclusion

Study results suggest that the longitudinal association between loneliness and dementia risk depends on epigenetic age. One implication of the current results is that the epigenome may be a promising area of study for understanding the processes through which loneliness increases dementia risk.
Loneliness as a risk factor for dementia
Authors: Echegut Marine Lea , Mukadam Naaheed , Shoham Natalie
Published: February 2022

Background

The importance of social relationships in health has been recognized over the years. Growing evidence in the field suggests that the feeling of loneliness, characterised by dissatisfaction with personal relationships, correlates positively with the outcome of dementia (Holwerda et al., 2014; Rafnsson et al., 2020; Sundström et al., 2020; Sutin et al., 2020). Systematic review has found mixed results but follow up times have generally been short and sample sizes small (Balouch et al., 2019; Penninkilampi et al., 2018).

Method

Using data from the UK Biobank, we will examine the association between loneliness and dementia. Between 2006 and 2010, twenty‐two recruitment centres have collected baseline data from over 500,000 participants all across the UK, providing socioeconomic and ethnic heterogeneity (Sudlow et al., 2015). This diversity in participants allows the generalisability of association between baseline characteristics and health outcomes (Sudlow et al., 2015). At baseline, all participants completed a mental health questionnaire which included questions about loneliness and quality of relationships. Our study will thus comprise the data of thousands of participants with a follow‐up of over 14 years.

We will use appropriate regression models, such as cox proportional hazard models, to study the impact of loneliness on the subsequent development of dementia, adjusting for age, sex, education, physical health and lifestyle factors, as well as social contact and quality of relationships.

Result

Data analysis is yet to be done. According to preliminary data analysis, we are expecting to find a positive correlation between loneliness and the onset of dementia, as illustrated by previous studies. We will conduct multiple cox proportional hazard models, adjusting for basic socio‐demographic, clinical and behavioural covariates. In addition, we will exclude all participants with a diagnosis of dementia within three years of baseline to eliminate reverse causation bias.

Conclusion

Loneliness as a risk factor for dementia.
“A brutal disadvantage for my wife [living with dementia] That has set us back years”: Results of a quantitative survey of caring relatives of people living with dementia during the Covid‐19 pandemic in Germany
Authors: Kowe Antonia , Teipel Stefan J
Published: February 2022

Background

The Covid‐19 pandemic poses a major challenge to the entire population. People living with dementia and their caring relatives, mostly older people, are considered a high risk group for infection with Covid‐19. As people living with dementia have a particular need for consistent daily routines and care, the restrictions during the pandemic presented relatives with new burden. Here, we investigated how caring relatives experienced the time during the Covid‐19 pandemic.

Method

We planned to conduct focus groups with different stakeholders in dementia care. Due to contact restrictions, we carried out a quantitative survey with a semi‐structured questionnaire as an alternative method of data collection. Questionnaires (n = 45) including open and closed questions were sent by post to the leaders of four self‐help groups for relatives of people living with dementia and then distributed to the members by the group leaders. We asked about the current health status of the respondents, the limitations during the Covid‐19 pandemic and changes in the care of people living with dementia.

Result

A total of 23 questionnaires were completed and returned to us. Participants had a mean age of 70.4 years (range 51 to 88 years). The majority of participants were female (69.6%). More than half of the participants assessed their health status as less good or bad (56.5%). Compared to the health status before the Covid‐19 pandemic, more than one third of respondents felt their own health was deteriorating (39.1%). Feelings of isolation and social exclusion increased in 39.1% of the participants during Covid‐19 pandemic. Most participants suffered from limitations of social contacts and leisure activities. The temporary closure of day care facilities for people living with dementia was a particular burden for caring relatives.

Conclusion

The majority of respondents experienced the Covid‐19 pandemic as burdensome with regard to their health and their care responsibilities. The statements of relatives underline the importance of maintaining clear structures in everyday life and in care of people living with dementia even in periods of crisis.
Public involvement to disseminate scientific findings in dementia care research: A quantitative survey on informal caregivers of people living with dementia
Authors: Kowe Antonia , Lüthje Corinna , Teipel Stefan J
Published: February 2022

Background

People living with dementia and their caring relatives can be involved in all phases of research, including the dissemination of research results. This involvement requires access to scientific findings and easily understandable results’ communication. Here, we investigated how informal caregivers of people living with dementia feel informed about the disease and how they want to be involved in the dissemination of research results.

Method

We surveyed informal caregivers of people living with dementia quantitatively with a semi‐structured questionnaire. Recruitment of participants was done through low‐threshold support groups of the local Alzheimer's Society. The questionnaire included open‐ended and closed‐ended questions on the subjective state of knowledge about dementia and the willingness to participate in the dissemination of scientific results. The data were analyzed descriptively.

Result

We sent 45 questionnaires by post with a response rate of more than one half (n = 23). The majority of participants (agemean = 70.4 years, 30.4% male) felt well informed about dementia (87.0%). Respondents who were willing to participate in the dissemination of research results (30.4%) wished to inform others in their private environment, e.g. friends or relatives. Respondents did not want to give lectures at scientific conferences or to be involved in writing articles for scientific journals.

Conclusion

The desire of the respondents to disseminate research results in the private environment could be met by appropriate peer training, which prepares informal caregivers of people living with dementia for low‐threshold communication of scientific findings. We may need to move away from the idea of integrating the public into science. Instead, we need to integrate science into the public and into the life of lay people.
Inter‐ and intra‐scanner variability of icobrain DM automated brain volumetry software on three different MRI systems
Authors: Wittens Mandy M.J. , Allemeersch Gert‐Jan , Sima Diana M. , Naeyaert Maarten , Vanderhasselt Tim , Vanbinst Anne‐Marie , Buls Nico , De Brucker Yannick , Raeymaekers Hubert , Ribbens Annemie , Smeets Dirk , Van Hecke Wim , Fransen Erik , Nagels Guy , Bjerke Maria , De Mey Johan , Engelborghs Sebastiaan
Published: February 2022

Background

Magnetic Resonance Imaging (MRI) has become part of clinical routine for diagnosis of neurodegenerative brain disorders. Acquisitions are performed at multiple centers, using multiple imaging systems and is therefore subjected to intra‐ and inter‐scanner variability. Detailed analysis of brain volumetry differences between MRI systems and scan‐rescan acquisitions can provide useful information to correct for different MRI scanner effects in future multi‐center longitudinal studies.

Method

The study population (n=10) consisted of five cognitively healthy controls and five patients belonging to different stages of the AD continuum. Subjects underwent brain MRI acquisitions on three different MRI systems with harmonized scan parameters: Philips Achieva dStream 1.5T, Philips Ingenia 3T and GE Discovery MR750w 3T. Sequences were harmonized by keeping acquisition parameters similar (Table 1). To test intra‐scanner variability, each participant underwent two subsequent MRI scans (between‐scan repositioning time 3‐5 minutes) per imaging system, repeated on three different MRI systems within two hours to test inter‐scanner variability. A total of 60 MRI scans were acquired for downstream comparative analysis. Brain volumes, including whole brain, (cortical) gray matter, hippocampal volumes, lateral ventricles, frontal, temporal and parietal cortices were computed with icobrain dm (v5.0). Coefficients of variation (CV), absolute volume differences (AVD), Dice similarity coefficients (DSC) and intraclass correlation coefficients (ICC) were computed to assess within‐ and between‐scanner agreement.

Result

The intra‐scanner CVs over all volumes were 0.948% for Discovery MR750w, 1.050% for Achieva and 1.152% for Ingenia. The inter‐scanner CVs were 3.016% for all‐scanner comparisons, 2.044% for Ingenia vs. Achieva, 3.191% for Achieva vs. GE and 3.326% for Ingenia vs. GE. The AVDs and ICCs were in line with the CV values. The intra‐scanner DSCs (mean±SD) over all volumes were 0.917±0.011 for Discovery MR750w, 0.917±0.010 for Achieva and 0.917±0.015 for Ingenia. The inter‐scanner DSCs were 0.898±0.017 for all‐scanner comparisons, 0.912±0.012 for Ingenia vs. Achieva, 0.888±0.013 for Achieva vs. Discovery MR750w and 0.893±0.015 for Ingenia vs. Discovery MR750w (Table 2, 3, Figure 1).

Conclusion

The variability results show an excellent agreement (CV<2%) for within‐scanner and a good agreement (CV<5%) for between‐scanner comparisons in terms of clinical relevance, indicating that MRI acquisition harmonization is beneficial for automated MRI volumetry software.
The experience of apathy in dementia: A qualitative study
Authors: Baber Waqaar , Chang Chern Yi Marybeth , Yates Jen , Dening Tom
Published: February 2022

Background

The presence of apathy is associated with less favourable outcomes in dementia, including more rapid functional and cognitive decline, greater disease severity and increased mortality. We aimed to explore and gain an understanding into how people with dementia experience apathy, and consequently suggest effective interventions to help them and their carers.

Method

12 participants (6 dyads of 6 people with dementia and their family carers) were recruited from memory cafés, social groups, seminars and Patient and Public Involvement (PPI) meetings. People with dementia and their carers were interviewed separately and simultaneously. Quantitative data was collected using the following validated scales: Apathy Evaluation Scale (AES), short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Montreal Cognitive Assessment (MOCA), Cornell Scale for Depression in Dementia (CSSD) and Hospital Anxiety and Depression (HAD). The interviews were semi‐structured, focusing on the subjective interpretation of apathy and impact on behaviour, habits, hobbies, relationships, mood and activities of daily living. Interviews were recorded and transcribed and analysed using interpretative phenomenological analysis (IPA) which generated codes and patterns, which were collated into themes.

Result

The participants with dementia had mild to moderate degrees of cognitive impairment, with a range between 9‐22 (out of 30) on the MOCA. They reported moderate levels of apathy on the AES.

Four superordinate themes were identified, three of which highlighted the challenging aspects of apathy: “Losing one’s sense of self”; “Feeling like a burden” and “Hindered by invisible obstacles”. One theme: ''What keeps me going’’, described the positive aspects of the individuals’ efforts to overcome apathy and remain connected with the world and people around them.

Conclusion

This study is the first to illustrate and conceptualise the subjective experience of apathy in dementia, portraying it as a more complex and active phenomenon than the traditional view of apathy being simply negative and hopeless. Our study reveals a struggle against cognitive difficulties, fear of failure and invisible obstacles, with individuals desperate to remain connected, and appreciative of their carers’ efforts to help them. Apathy and its effects warrant more attention from clinicians, researchers and others involved in dementia care.
Predictability of polygenic risk score for progression to dementia and its interaction with APOE ε4 in mild cognitive impairment
Authors: Pyun Jung Min , Park Young Ho , Lee Keon‐Joo , Kim Sangyun , Saykin Andrew J. , Nho Kwangsik
Published: February 2022

Background

The combinatorial effect of multiple genetic factors calculated as a polygenic risk score (PRS) has been studied to predict Alzheimer’s disease (AD) risk and evidence suggests that the predictability of PRS can be affected by the presence of APOE e4 allele substantially. Therefore, we aimed to evaluate the predictability of PRS on disease progression to AD depending on APOE ε4 carrier status and its interaction with APOE ε4 in mild cognitive impairment (MCI).

Method

We analyzed 732 MCI patients from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort with those who progressed to AD within 5 years post‐baseline (n=270) and remained stable as MCI (n=462). The predictability of PRSs including and excluding the APOE region (PRS+APOE and PRS‐APOE) on the conversion to AD and its interaction with APOE ε4 carrier status were assessed using Cox regression analyses. Gene set enrichment analysis of single nucleotide polymorphisms (SNPs) selected for PRS calculation was performed.

Result

PRS+APOE (hazard ratio (HR) 1.468, 95% CI 1.335–1.615) and PRS‐APOE (HR 1.293, 95% CI 1.157–1.445) both were associated with a significantly increased risk of progression to dementia in MCI (Table 1). The interaction between PRS+APOE and APOE ε4 carrier status was significant with a p‐value of 3.78×10‐2 (Table 2). The association of PRSs with progression risk was stronger in APOE ε4 non‐carriers (PRS+APOE: HR 1.710, 95% CI 1.244–2.351, PRS‐APOE: HR 1.429, 95% CI 1.182–1.728) than APOE ε4 carriers in MCI (PRS+APOE: HR 1.167, 95% CI 1.005–1.355, PRS‐APOE: HR 1.172, 95% CI 1.020–1.346) (Table 1 and Figure 1). Gene set enrichment analysis identified 27 significant pathways including those linked to amyloid, lipid, and protein metabolisms (Figure 2).

Conclusion

The results demonstrated that PRSs showed a significant interaction with APOE ε4 carrier status and PRSs including and excluding APOE regions could predict conversion of MCI to dementia with a stronger association in APOE ε4 non‐carriers than APOE ε4 carriers. This indicates PRS as a potential genetic predictor particularly for progression of MCI patients with no APOE ε4 alleles.
The influence of genetic predisposition for Alzheimer's disease on default mode network co‐activation in young adults: A Human Connectome Project replication study
Authors: Mentink Lara J. , Guimarães João P.O.F.T. , Sprooten Emma , Olde Rikkert Marcel G.M. , Haak Koen V. , Beckmann Christian F.
Published: February 2022

Background

A landmark study by Filippini et al., where authors reported an increased default mode network (DMN) co‐activation during rest in young APOE ε4‐carriers, failed to replicate [1,2]. The rise of genome‐wide association studies (GWAS) in Alzheimer’s disease (AD) has shown there is a significant polygenic contribution of common genetic variants to AD, in addition to the larger effects of APOE variants. Therefore, in our replication study, we used polygenic risk scores (PRS) to better understand how polygenic variation may influence brain structure and function.

Method

We included participants with inferred European ancestry from the HCP S1200 dataset. We followed the methods of [1] for the resting‐state fMRI analysis. For structural MRI analysis, we assessed gray matter volume with FreeSurfer instead of gray matter density using voxel‐based morphometry. PRS allows data‐driven investigation of the aggregated effects of many common risk variants as determined in a large European GWAS [3]. We used the threshold determined as optimal for predicting AD status using PRS in Jansen et al., (P<1.69x10‐5). Permutation Analysis of Linear Models (PALM) was used to test the association between PRS and both DMN co‐activation and gray matter volume. PALM controls for biases induced by the family structure of the HCP sample. Results were family‐wise error rate corrected at p < 0.05.

Result

There was no significant association between DMN co‐activation and PRS (N=454). For the morphometric analyses (N=625), no association between gray matter volume and PRS was found. For both analyses, including covariates (different combinations of age, sex, education level, head motion) did not alter the results.

Conclusion

We did not find evidence that genetic predisposition for AD, indicated by PRS, impacts DMN co‐activation in young adults. However, we may not be able to find any measurable effect decades before a clinical expression of AD. Repeating the analysis in an older cohort will inform us whether the influence of genetic predisposition for AD changes with age. 1) Filippini et al., PNAS, 2009. 2) Mentink et al., Default mode network co‐activation in young APOE ε4‐carriers: a Human Connectome Project replication study. AAIC 2020. 3) Jansen et al., Nature Genetics, 2019
Examining the carer‐related and patient‐related factors predicting anxiety amongst family carers of people with dementia
Authors: Van Hout Elien , Contreras Milena L , Mioshi Eneida , Kishita Naoko
Published: February 2022

Background

Anxiety in family carers of people with dementia has been neglected in research, although its prevalence may be similar or even greater to that of depression. The current literature has also demonstrated that existing interventions tend to be less effective for anxiety than for depression or burden in family carers. Therefore, it is important to identify factors affecting carer anxiety to inform the development of future interventions. The aim of this study was to determine which carer‐related (age, gender, hours of caring per week, comorbidities, sleep quality) and patient‐related (dementia severity based on functional deterioration, neuropsychiatric symptoms of dementia) factors known to have an impact on carer wellbeing predict anxiety amongst family carers of people with dementia.

Method

This study used a cross‐sectional design with a sample of ninety‐one family carers, with a mean age of 69.46 years old. More than 65% of carers were female and were living together with the care recipient. Most of care recipients were in the severe stages of Alzheimer’s disease. First, a single regression analysis with each potential independent variable was conducted. The independent variables that passed a certain p‐value threshold (carer age, carer gender, hours of caring per week, sleep quality, neuropsychiatric symptoms) were then included in the final multiple regression model. Due to significant multicollinearity, dementia severity was excluded from the final regression model.

Result

The final regression model (R²=0.29) demonstrated that the numbers of hours providing care (β=.24) and sleep quality (β=.28) had a significant impact on carer anxiety.

Conclusion

Providing more hours of care per week and having worse sleep quality seem to predict higher levels of anxiety in family carers. Studies exploring factors, which could moderate the impact of hours of caring and sleep quality, may further guide future interventions. The relationship between sleep quality and anxiety also requires attention as some studies have reported that sleep quality may be bidirectionally related to anxiety. That is, successful treatment of sleep disturbances may prevent exacerbation of anxiety and vice versa. Future research should further investigate the impact of sleep quality in family carers, ideally using a longitudinal design.
Phenotype‐dependent relationships between cortical macro‐ and micro‐structural neurodegeneration in frontotemporal lobar degeneration
Authors: Placek Katerina , Anania Vincenzo , Van Phan Thanh , de Barros Nuno Pedrosa , Billiet Thibo , Ribbens Annemie , Simen Arthur , Schwarz Adam J.
Published: February 2022

Background

Macro‐ and micro‐structural degeneration in cortical grey matter (CGM) accompany the progression of frontotemporal lobar degeneration (FTLD). The former can be measured by brain volumetry from magnetic resonance imaging (MRI) and the latter by mean diffusivity (MD) from diffusion tensor imaging (DTI). While disease‐modifying treatment is expected to slow the progression of both metrics, unexpected treatment effects such as inflammation may alter the relationship between them. Here, we evaluate the cross‐sectional and longitudinal relationships between lobar volume and average MD of CGM in untreated FTLD.

Method

24 patients with behavioral variant frontotemporal dementia (BV), 21 with semantic variant primary progressive aphasia (SV), 20 with nonfluent agrammatic variant primary progressive aphasia (PNFA), and 75 cognitively‐normal controls (CON) from the FTLD Neuroimaging Initiative (FTLDNI) were assessed longitudinally with MRI and DTI. CGM volumes were measured with icobrain dm using T1‐weighted and FLAIR images. CGM MD maps were extracted from DTI and partial‐volume corrected. Volume and average MD were calculated for each lobe using two timepoints approximately 1 year apart, adjusted for age and sex, and z‐scored relative to CON. For each lobe, multiple linear regression models with Bonferroni correction assessed the effect of FTLD phenotype on the relationship between 1) baseline MD and volume, and 2) percent change from baseline in MD and volume.

Result

At baseline, BV, SV, and PNFA demonstrated significantly more negative associations between MD and volume in the frontal lobes relative to CON (all p values <.05), such that greater MD related to lesser volume in each phenotype. Significantly more negative associations between MD and volume relative to CON were observed for BV and SV in the temporal lobe, and for PNFA in the parietal lobe (p <.05). For percent change from baseline, BV demonstrated a significantly more negative association between MD and volume in the frontal and parietal lobes relative to CON (p <.05), such that percent increase in MD related to percent decrease in volume.

Conclusion

Our results elucidate phenotypic differences in cortical macro‐ and micro‐structural degeneration in FTLD and provide a novel frame of reference for MRI and DTI for interventional clinical trials.
Implementation of multi‐contrast, multi‐echo SAGE‐fMRI in aging and Alzheimer's disease
Authors: Keeling Elizabeth G. , Bergamino Maurizio , Burke Anna D. , Steffes Lori , Stokes Ashley M.
Published: February 2022

Background

An advanced spin‐ and gradient‐echo (SAGE) functional MRI (fMRI) sequence was implemented in healthy aging control (HC) and cognitively impaired (CI) groups to improve functional assessment of AD‐relevant regions susceptible to signal dropout in standard fMRI.

Method

Five HC and four CI were included in this preliminary study. SAGE‐fMRI data were acquired at 3T (Ingenia, Philips) with 2 gradient‐echoes (GRE), 2 asymmetric spin‐echoes (SE), and 1 spin‐echo (TE1‐5 = 5.97/18.76/36.048/49.27/62.06 ms, acquisition matrix: 64×64; voxel size: 3.75x3.75 mm; slice thickness: 5.0 mm; TR=3000 ms). SAGE‐fMRI data were processed using single‐echo and multi‐echo combinations and weighted (w) summations (GRE (macrovascular): TE2, T2*, wT2*; SE (microvascular): TE5, T2, wT2). Specifically, TE2 (similar to standard fMRI) and TE5 were processed individually. Dynamic T2
*and T2 were fit using a piece‐wise function, while weighted summations for wT2
*and wT2 were calculated as previously described. Subsequently, all SAGE‐fMRI images were processed using standard procedures with FSL and AFNI. Face‐name memory encoding and recall tasks conditions were organized in alternating block designs and consisted of novel (unfamiliar faces) and repeated (one of two recurring faces) phases, with brief rest periods between conditions. AFNI was used to calculate the statistical parametric maps of response to stimuli from all fMRI data (3dDeconvolve) and to run a two‐sample t‐test between HC and CI groups (3dttest++).

Result

HC showed increased activation compared to CI for memory encoding and recall tasks across each SAGE‐fMRI analysis method. Weighted summation SAGE contrasts showed robust differences between groups in the cingulate gyrus and frontal pole in the memory encoding task. Moreover, the frontal pole had sizeable differences between groups in memory recall, particularly in the microvascular contrasts; these weighting factors revealed more distinct differences between groups across regions of interest for the memory recall task than the macrovascular contrasts. Notably, in the memory recall task, T2* and T2 distinguished between groups in AD‐relevant regions such as the hippocampus and parahippocampal gyrus where single‐echo fMRI did not.

Conclusion

Preliminary results reveal widespread decrease in task‐related activation from HC to CI groups, with further distinction between the two groups in AD‐relevant regions such as the hippocampus and parahippocampal gyrus via SAGE‐fMRI.