bluuebunny/crossref_metadata_2025 huggingface dataset:
Early detection of Alzheimer's disease using 3D convolutional neural networks
Authors: Pan Dan , Zeng An , Zou Chao , Rong Huabin , Song Xiaowei
Published: February 2022

Background

As one of the most common neurodegenerative disorders which progress slowly over time, Alzheimer's Disease (AD) could be effectively managed by delaying the disease process through early detection and intervention at present. Mild Cognitive Impairment (MCI) is the prodromal state of AD. At present, in‐vivo structural magnetic resonance imaging (MRI) has been widely used for computer‐aided diagnosis of neurodegenerative disorders noninvasively owing to its sensitivity to morphological changes caused by brain atrophy like AD. Plus, the rapid progress of deep learning (DL), especially deep convolutional neural networks (CNNs) has improved MRI analysis thanks to its superiority in the generalization capability.

Method

An ensemble learning (EL) model which combines genetic algorithm (GA) with 3D‐CNN based on region of interest (ROI) was proposed to identify AD/MCI subjects (Figure 1). We firstly used the 3D‐CNN model to train a candidate base classifier for each a ROI (here a brain region). Then, the GA algorithm was employed to search for the best base classifier combination with the optimal generalization ability and based on it, the whole‐brain MRI classifier ensemble was built to detect AD/MCI. Owing to the one‐to‐one correspondence relationship between the base classifiers and the brain regions, we further identified those brain regions with significant classification capabilities.

Result

In three binary classification tasks, i.e., classification between 1) AD vs. NC (Normal control), 2) MCIc (MCI patients who will convert to AD) vs. NC and 3) MCIc and MCInc (MCI patients who will not convert to AD), the testing results revealed accuracy rate of 0.89±0.03, 0.88±0.03, and 0.71±0.08, with a stratified fivefold cross‐validation method, respectively. In a data‐driven way, the brain regions that greatly contributed to AD and MCI classifications (Figure 2), e.g., medial amygdala, rostral hippocampus, caudal hippocampus, were ascertained. They were linked to emotion, memory, language, and other key brain functions impaired early in the AD staging.

Conclusion

Compared with the 2D‐CNN models, the proposed classifiers ensemble could make full use of the effective information embedded in MRI to discover more discriminative MRI features/biomarkers. Additionally, the advocated method could also be valuable to detect the potential neuroimaging biomarkers for other brain disorders.
18F‐MK6240 longitudinal tau PET in ageing and Alzheimer’s disease
Authors: Krishnadas Natasha , Dore Vincent , Mulligan Rachel S. , Tyrrell Regan , Bozinovski Svetlana , Huang Kun , Lamb Fiona , Burnham Samantha C. , Villemagne Victor L. , Rowe Christopher C.
Published: February 2022

Background

Longitudinal tau PET may prove useful for clinical trials, through its ability to detect patterns and rates of in vivo tau accumulation in ageing and Alzheimer’s disease (AD). Clinical trials are increasingly targeting the preclinical phase of AD. Flortaucipir studies estimate a 3% annual increase in global cortical tau SUVR in amyloid‐β positive (Aβ+ve) cognitively impaired (CI) cohorts, whereas either no change, or low rates of increase (0.5%), have been demonstrated in Aβ+ve cognitively unimpaired (CU) cohorts. F‐18 MK6240 is a novel tau tracer, with high target to background binding. We aimed to evaluate regional rates of 18F‐MK6240 accumulation in ageing and the AD continuum.

Method

We performed PET acquisition 90‐100 minutes post‐injection of 185MBq (±10%) 18F‐MK6240 at baseline and 12 months for 67 Aβ‐ve CU, 20 Aβ+ve CU and 19 Aβ+ve CI participants. SUVR (standardized uptake value ratio) for the entorhinal cortex, amygdala, hippocampus, parahippocampus and composite regions of interest (ROI) (Me, mesial temporal; Te, temporoparietal cortices) were generated using the cerebellar cortex as the reference region.

Result

Age did not significantly differ between the groups (mean age 74 ± 4.4 Aβ‐ve CU, 76.2 ± 5.7 Aβ+ve CU, 72.5 ± 6.4 Aβ+ve CI). Aβ+ve participants (CU and CI) had higher baseline tau SUVR and higher annual percentage increases in tau SUVR compared to Aβ‐ve participants in all regions examined (Table 1) (Figure 1). CU Aβ+ve participants had larger increases in Me vs Te (1.6% vs 0.7%), while CI Aβ+ve participants had larger increases in Te vs Me (4.3% vs 1.9%). Compared to Aβ‐ve CU participants, Aβ+ve CU participants had higher increases in the amygdala (2.9% vs 1.8%) and entorhinal cortex (1.9% vs 0.7%).

Conclusion

Longitudinal tau imaging using 18F‐MK6240 discriminates between ageing and stages of AD. Rate of accumulation in preclinical AD (Aβ+ve CU) was highest in mesial temporal regions, while in CI individuals, rates were highest in the temporoparietal cortex. The amygdala and entorhinal cortex may be early regions to discriminate tau accumulation between Aβ‐ve CU and Aβ+ve groups. However, as the variance is large, the precision of these estimates may be refined with a larger sample size. Recruitment is ongoing.
Identifying precision AD biomarkers with varying prognosis effects in genetics driven subpopulations
Authors: Lee Brian N. , Wang Junwen , Shen Li
Published: February 2022

Background

Imaging, cognitive and fluid data have been widely studied to identify quantitative biomarkers that can help predict the status and progression of Alzheimer’s disease (AD). However, it is still an underexplored topic whether there exist subpopulations with different genetic profiles across which the biomarker‐based prediction models may vary. We propose to use the Chow test (Chow 1960 Econometrica 28(3)) to perform genetically stratified analyses for identifying SNP‐based subpopulations coupled with precision AD biomarkers with varying effects on future diagnosis in these subpopulations. The investigation of such SNPs and precision biomarkers may eventually pave the way for increased customization of AD care.

Method

Participants included 1,324 subjects from the ADNI cohort with both AD biomarker and genotyping data available (http://www.pi4cs.org/qt‐pad‐challenge). 30 significant (P < 1.5E‐278) AD SNPs were sourced from (Jansen 2019 NatGen). Chow tests were performed to determine whether each of baseline visit measures of 16 AD biomarkers predicted AD diagnosis at the three‐year visit with varying slopes when stratifying upon the allelic dosage of each of 30 chosen SNPs. Bonferroni correction (P < 1.04E‐4) was employed to correct for multiple comparisons.

Result

Multiple SNP‐biomarker pairs showed significant genetically driven deviations in the regression coefficients when predicting diagnosis in three years using baseline biomarkers (Figure 1). Top SNP hits involved rs769449 (Chr 19, APOE) and rs7561528 (Chr 2, LOC105373605), and almost all 16 studied biomarkers demonstrated differential slopes in different genotype groups to predict diagnosis in three years. To examine the details of these top findings, the regression coefficients calculated for each of the five most significant biomarkers of both SNPs were bootstrapped and plotted in Figure 2.

Conclusion

Genetic analysis of AD candidate SNPs in conjunction with AD biomarker data via the Chow test identified several SNPs coupled with precision AD biomarkers with varying prognosis effects in the corresponding genotype groups. These findings provide valuable information to reveal disease heterogeneity and help facilitate precision medicine.
Development and evaluation of MIITRA T1w and DTI brain templates at 0.5 mm resolution
Authors: Wu Yingjuan , Niaz Mohammad Rakeen , Ridwan Abdur Raquib , Qi Xiaoxiao , Bennett David A. , Arfanakis Konstantinos
Published: February 2022

Background

An MRI multimodal older adult brain atlas with high spatial resolution is in high demand. As part of the Multichannel Illinois Institute of Technology & Rush university Aging (MIITRA) atlas project, this work aimed to develop high quality 0.5mm resolution T1‐weighted (T1w) and diffusion tensor imaging (DTI) multimodal templates using data from a large, diverse, community cohort of non‐demented older adults and quantitatively evaluate the new templates.

Method

Template construction: T1w and DTI data were collected on 400 non‐demented older adults (50% male;64.9‐98.9 yrs;54% white,43% black) participating in longitudinal cohort studies of aging (Bennett et al.,2018; Barnes et al.,2012) with two 3T MRI scanners.

First, a recently introduced approach for the development of high quality multimodal templates (Wu et al., 2019) was conducted in a 0.5mm isotropic resolution space to maximize the quality and anatomical consistency of the templates. Then an approach for the development of high spatial resolution templates based on principles of super‐resolution (Niaz et al., 2019) was used to eliminate interpolations in conventional template building methods. The resulting templates are named MIITRA templates. Evaluation: T1w and DTI data on 202 non‐demented older adults from ADNI3 were used for evaluation. The MIITRA templates were compared to other standardized templates in terms of the accuracy of inter‐subject spatial normalization and inter‐modality spatial matching of ADNI3 data achieved when each template was used as a reference for normalization.

Result

Visual inspection shows that the MIITRA T1w and DTI templates with 0.5mm isotropic voxels exhibit high sharpness and are free of artifacts (Fig. 1, 2). Figures 3 and 4 demonstrate that the MIITRA templates provided higher inter‐subject spatial normalization accuracy of older adult data and required less deformation than other templates. Finally, the MIITRA T1w and DTI templates exhibited high spatial matching to each other and allowed higher inter‐modality spatial matching of normalized older adult data (Fig. 5).

Conclusion

This work developed high quality 0.5mm resolution T1w and DTI templates for the MIITRA atlas using data from a large, diverse, community cohort of non‐demented older adults. The new templates allowed higher inter‐subject and inter‐modality spatial normalization of older adult data compared to other templates.
Cultural adaptation of the Reducing Disability in Alzheimer’s Disease (RDAD) protocol for intervention to reduce behavioral and psychological symptoms of dementia (BPSD) in Thailand
Authors: Thongsiri Sirinart , Chuengsatiansup Komatra , Sihapark Siranee , Wisetpholchai Bussabong , Luechai Rusamee , Teri Linda , Wandersman Abraham , Lamont Andrea , Fritz Stacy , Marques Andrea Horvath , Hinton Ladson , Gallagher‐Thompson Dolores , Chen Hongtu , Levkoff Sue E
Published: February 2022

Background

The Reducing Disability in Alzheimer’s Disease (RDAD) protocol is an evidence‐based intervention (EBI) found to be feasible for implementation in community settings, and effective for reducing behavioral and psychological symptoms of dementia (BPSD) and improving caregiver outcomes (Teri et al., 2003; 2008). This study adapted the RDAD for delivery in Thai community settings, so that core components of the intervention—knowledge, communication, pleasant events, behavioral modification and physical activity—could be implemented through home‐based care by community‐based health personnel.

Method

Adaptation processes followed, sometimes recursively, 10 adaptation steps identified by Escoffery et al., (2018): (1) assess the current care delivery system and resources in the community, (2) understand relevant EBIs, (3) select appropriate EBI, (4) consult with experts in intervention design and implementation, (5) consult with stakeholders in implementation settings, (6) work with experienced implementers to decide what needs to be adapted, (7) adapt original intervention program, (8) train staff for implementation of modified intervention, (9) test adapted materials, and (10) implement and evaluate intervention.

Result

Based on qualitative data collected through consultation and discussion meetings with experts in intervention and implementation research and stakeholders of care delivery from local communities (Steps 1‐7), a modified Thai‐RDAD protocol was developed to fit into the clinical, social, and cultural practice of Thai local settings. Protocols for training were pilot tested with 20 providers (Steps 8); and the Thai‐RDAD protocol was tested with persons with dementia and their family caregivers at four participating families (Step 9). Findings from the pilot study were incorporated into the intervention protocol, particularly concerning comprehension of the intervention activities, realistic goal setting, and improving communication among all parties involved, prior to implementation (Step 10) of the adapted intervention protocol in an NIMH‐funded large clinical trial in the long‐term care system of Thailand.

Conclusion

A systematic approach to adaptation of EBIs by synthesizing perspectives from both intervention and implementation researchers, as well as stakeholders of care delivery from local communities, and pilot testing the modified EBI protocol, are critical for effective adaptations to local clinical and cultural contexts.
Associations between mean apparent propagator MRI and cerebrospinal fluid markers of AD pathology, neurodegeneration, and glial activation, in cognitively unimpaired adults
Authors: Moody Jason F. , Dean Douglas C. , Kecskemeti Steven R. , Blennow Kaj , Zetterberg Henrik , Carlsson Cynthia M. , Johnson Sterling C. , Alexander Andrew L. , Bendlin Barbara B.
Published: February 2022

Background

Numerous studies have reported correlations between diffusion tensor imaging (DTI) metrics and cerebrospinal (CSF) biomarkers of Alzheimer’s disease (AD) pathology. However, the assumption of Gaussian diffusion in DTI limits the ability to characterize white matter (WM) microstructural changes. Mean apparent propagator (MAP) MRI is a model that attempts to overcome this limitation by allowing for the estimation of parameters that convey more precise information about WM microstructure.

To investigate MAP MRI’s sensitivity to early WM degeneration associated with preclinical, asymptomatic AD pathology, we examined the relationship between CSF biomarkers and MAP MRI microstructural parameters in 92 cognitively unimpaired adults.

Method

92 cognitively unimpaired controls from the Wisconsin Registry for Alzheimer’s Prevention and the Wisconsin Alzheimer’s Disease Research Center were imaged with multi‐shell diffusion‐weighted MRI. DTI metrics (FA, MD, RD, AxD) were computed and the MAP MRI model was employed to calculate various microstructural parameters: Return to origin probability (RTOP), return to axis probability (RTAP), return to plane probability (RTPP), mean squared displacement (MSD), Non‐Gaussianity (NG), and q‐space inverse variance (QIV). DTI and MAP parameter values were extracted from the cingulum and correlated to Aβ42, P‐Tau, P‐Tau/Aβ42, YKL‐40, and neurofilament light chain (NFL) levels in lumbar cerebrospinal fluid samples.

Result

MAP parameters were moderately and significantly correlated to most CSF measures. RTPP was significantly correlated to all 5 CSF measures, while MSD, NG, and QIV were significantly correlated to 4 of 5 CSF measures. NFL, a known marker for axonal degeneration, was significantly related to 5 of the 6 MAP parameters assessed. Meanwhile, correlations between DTI and CSF measures were weak and non‐significant.

Conclusion

These preliminary results highlight the potential of MAP MRI to detect early WM deterioration indicative of preclinical, asymptomatic AD and associated neurodegeneration. MAP metrics extracted from a commonly affected WM tract in AD were more strongly and significantly correlated with CSF measures than DTI metrics were, suggesting that MAP MRI may be more useful than DTI for identifying the earliest WM microstructural changes associated with AD. Future work will incorporate longitudinal data and assess the effects of CSF and molecular imaging markers on MAP age trajectories.
The Mediterranean diet and physical activity: A cross‐sectional analysis of the Maintain Your Brain randomised controlled trial
Authors: Ghacham Ali , Noble Yian , Rangel Carolina Almendrales , Mavros Yorgi , Radd‐Vagenas Sue , Sabeti Neda , Heffernan Megan , Brodaty Henry , Sachdev Perminder S , Lautenschlager Nicola T , Singh Maria A Fiatarone , O'Leary Fiona
Published: February 2022

Background

Dementia has no pharmacological cure. Therefore, lifestyle interventions targeting modifiable risk factors to reduce cognitive decline are of interest. This study examines the cross‐sectional relationships between two potentially protective behaviours: Mediterranean diet (MediDiet) adherence and physical activity (PA).

Method

Participants were recruited from the Sax Institute’s 45 and Up Study into the Maintain Your Brain trial. MediDiet adherence was assessed using the validated Mediterranean Diet and Culinary Index (MediCul) tool. The 50‐item tool consists of 17 sub‐categories focusing on key aspects of the MediDiet. Leisure time PA was assessed by a standard questionnaire and intensity was quantified using the BORG Rating of Perceived Exertion (RPE) scale, modified for strength and aerobic activities. Associations between the MediDiet and PA were investigated using hierarchical linear regression and analysis of covariance.

Result

6236 participants [55‐77 years; mean (SD)=65.0 (5.8)] completed baseline assessments and were included. Mean (SD) MediCul score was 53.2 (13.0)/100), indicating low adherence to the MediDiet. Only 5% of participants achieved a score consistent with better cognitive outcomes in The PREDIMED study. Almost one‐half of participants (48.4%) met aerobic PA (150 min/week) but less than one‐quarter (24.2%) met resistance training (RT) recommendations (2 days/week). Unadjusted MediCul score explained a small but significant amount of the variance for light (1.0%) and moderate‐vigorous (MV) (3.1%) PA, both p<0.001. For light PA, the final model, including MediCul, age, sex, BMI, CAGE (alcohol use) score and diabetes explained 2.8% of the variance. For MV PA, the final model including MediCul, age, sex, BMI, CAGE, depression, diabetes and education explained 10.9% of the variance. A 10‐point higher MediCul score was associated with an additional 3.3 seconds of light PA/wk and additional 7.5 seconds of MV aerobic PA/wk (both p<0.001). Additionally, MediCul score was significantly higher in participants engaging in 2+days/wk of RT compared to 1 or fewer days/wk (56.6/100 vs. 52.2/100, respectively; p<0.001).

Conclusion

Both aerobic and RT PA are significantly but weakly associated with better diet, but the clinical meaningfulness, as well as any causal nature, of these relationships requires further exploration. The outcomes of the MYB trial will contribute substantively to this question.
The predictive factors of dementia conversion in amyloid‐negative amnestic mild cognitive impairment
Authors: Kim Hyung‐Ji , Lee Jae‐Hong , Jo Sungyang , Lee Sunju
Published: February 2022

Background

Around 15–20% of patients with clinically probable Alzheimer’s disease have been found to have no significant Alzheimer’s pathology on amyloid PET. A previous study shows that conversion to dementia from amyloid‐negative mild cognitive impairment (MCI) was observed in up to 11% of patients, drawing attention to this condition. We gathered the detailed neuropsychological and neuroimaging data of this population to elucidate factors for conversion to dementia from amyloid‐negative amnestic MCI.

Method

This study was a retrospective cohort study of patients over the age 50 with amyloid‐negative amnestic MCI who visited the memory clinic of Asan Medical Center with no less than a 36 months follow‐up period. All subjects underwent detailed neuropsychologic tests, three tesla brain magnetic resonance imaging (MRI) scans including 3‐dimensional T1 imaging, and fluorine‐18[F18]‐florbetaben amyloid PET scans.

Result

During the 36 months of follow‐up, 39 of 107 (36.4%) patients converted to dementia from amnestic MCI. The volumetric analysis revealed that the converter group had significantly reduced total hippocampal volume on the right side, gray matter volume in the right lateral temporal, lingual gyri, and occipital pole. In terms of cerebellar gray matter (GM) volumetric analysis, reduced Crus I/II volume adjusted with total intracranial volume (TIV) and age was observed in the converter group. The converter group had also more severe impairments in all visual memory tasks.

Conclusion

Our study showed that the reduced gray matter volume related to visual memory processing in the cerebrum and Significant cerebellar GM atrophy involving the bilateral Crus I/II may predict the clinical progression in this amyloid‐negative MCI population.
Cortical remodeling across the lifespan in healthy brain reveals structural network vulnerability to neurodegeneration
Authors: Agosta Federica , Basaia Silvia , Cividini Camilla , Spinelli Edoardo Gioele , Castelnovo Veronica , Leocadi Michela , Calderaro Davide , Magno Maria Antonietta , Canu Elisa , Filippi Massimo
Published: February 2022

Background

Aging is the main risk factor for most of the neurodegenerative diseases. The aim of this study was to investigate typical cortical thinning changes across lifespan in the healthy brain revealing structural network vulnerability to neurodegeneration.

Method

The cohort included 128 healthy individuals aged 20‐85 years that underwent an MRI scan. Structural T1‐weighted images were used to estimate vertex‐wise cortical thickness maps, then grouped into 83 regions. For each region, cortical thickness trajectory with advancing age was estimated, including sex as covariate. Additionally, all regions were ranked based on their relative thickness at the end of the observed lifetime, assessing regional changes over time. Finally, regional mean thickness was correlated with relative change over time.

Result

The highest cortical thinning was observed in the temporal lobe (parahippocampal, entorhinal, superior and middle temporal and fusiform), in the frontal lobe (lateral orbitofrontal, superior and inferior frontal and rostral anterior cingulate), in the parietal lobe (the isthmus of cingulate, precuneus, supramarginal and inferior parietal) and in the insular cortex. Interestingly, occipital regions (cuneus, lateral occipital, lingual, pericalcarine), and motor and premotor areas (precentral, postcentral and paracentral regions) showed the least cortical thickness change relative to the whole brain. Finally, positive correlation was found between mean regional thickness and its relative change over time.

Conclusion

This study highlights structural vulnerability of brain regions to aging. Furthermore, results provide information concerning trajectories of normal brain aging, identifying those areas that might be more vulnerable to the attack of neurodegeneration. Supported by: European Research Council (StG‐2016_714388_NeuroTRACK).
Baseline associations of cardiometabolic risk factors, executive function, and white matter microstructure in the DIRECT‐PLUS trial
Authors: Kaplan Alon , Beyer Frauke , Witte A. Veronica , Shai Iris
Published: February 2022

Background

Cardiometabolic risk factors including mid‐life obesity, diabetes and hypertension are associated with accelerated cognitive decline, e.g. in executive function, and brain aging, e.g. alterations in white matter (WM) microstructure [1].

Method

290 participants (34 females, mean age= 49 y (30 – 79 y) of the DIRECT‐PLUS trial (clinicaltrials.gov ID: NCT03020186, [2]) participated in diffusion‐weighted imaging on a 3T Philips. Tract‐based spatial statistics provided hemisphere‐averaged fractional anisotropy (FA) of 9 fiber tracts (genu/body of corpus callosum, body and crus of fornix, (hippocampal) cingulum, inferior/superior longitudinal fasciculus (i/sLF) and uncinate fasciculus. We tested the association of age, sex, five risk factors (body mass index (BMI), systolic blood pressure (SBP), glycated hemoglobin, high and low‐density lipoprotein), four measures of executive function from the brief executive function battery and average FA of these WM tracts with correlations and linear regression models, adjusting for age and sex, in R version 3.6.1, corrected for multiple testing using false discovery rate (FDR).

Result

Age was associated with lower FA in the cingulum (r=‐0.56, p<0.001), uncinate fasciculus (r=‐0.51, p<0.001), hippocampus cingulum (r=‐0.39, p<0.001), iLF (‐0.19, p=0.001) and sLF (r=‐0.18, p=0.001). FA in the fornix, hippocampus cingulum and iLF were higher in men as compared to women (p<0.05 for all). Among cardiometabolic risk factors, higher BMI was associated with significantly lower FA in iILF (β = ‐0.002, p=0.0009, padj=0.035), and higher SBP was associated with lower FA in uncinate fasciculus (β= ‐0.0006, p=0.0012, padj=0.035)None of the executive function measures was significantly related to FA of WM tracts after adjusting for age and sex and controlling for FDR.

Conclusion

Our findings corroborate previous findings of the adverse impacts of cardiometabolic risk on WM microstructure. Upcoming longitudinal investigations in this dataset will show whether improved cardiometabolic function, induced by a dietary intervention, will modify the trajectories of WM microstructure and cognitive performance. Figure 1: Higher BMI and higher SBP were significantly associated with lower FA in two major WM tracts (blue: ILF, green: uncinate fasciculus)[1] Wassenaar, TM., et al. NBA (2019) [2] Tsaban, G, et al. Heart (2020).
Effects of cognitive training on memory in SCD and MCI participants: Preliminary results of a single‐blind RCT comparing a web‐based application and a narrative videogame
Authors: Nieto‐Vieites Ana , Pérez‐Blanco Lucía , Mallo Sabela C. , Campos‐Magdaleno Maria , Felpete Alba , Lojo‐Seoane Cristina , Cid‐Fernández Susana , Juncos‐Rabadán Onésimo , Pereiro Arturo X
Published: February 2022

Background

Cognitive training has been found to be effective in preventing and delaying cognitive decline in MCI and early dementia, and gains could be enhanced with transcranial electrical stimulation (tDCS). Cognitive‐training applications (app) allow remote interventions, optimize the cost‐benefit ratio, and a continuous monitoring. Most of apps are web‐based applications but specific narrative cognitive‐training video‐games are scarce. Our RCT aims to compare memory changes after training using a web‐based app (i.e., NeuronUp) and a narrative video‐game (i.e., ‘Following the traces of time’) combining with tDCS or Sham (placebo).

Method

Fifty‐three participants with SCDs and MCI were randomized assigned to the five experimental groups (i.e., Active‐control=11; NeuronUP‐tDCS=14; NeuronUP‐Sham=9; Videogame‐tDCS=9; Videogame‐Sham=10). NeuronUP groups sequentially performed 24 computerized activities (in 8 activities/session cycles) with increasing in complexity according actual performance. Videogame groups resolved puzzles with three difficulty levels integrated into a meaningful narrative plot allowing them to advance in the story. NeuronUP and Videogame mainly implemented memory and executive function training. The active‐control group attended specific classes for older people (i.e., computing and mildfulness/philosophy). All interventions extended along 20 hours (5 weekly sessions of 120 min for 2 weeks) and participants simultaneously received 20’ of tDCS/Sham in the last 6 sessions.

Pre‐Post assessments were accomplished to tests changes in measures of immediate verbal recall (Lists A and B of the RAVLT), and prospective memory (Forms 1 and 2 of the Event‐Related Task; MPMT).

Results

Repeat measures ANOVA showed that Immediate recall (Figure 1) significantly improved in post‐intervention, F(1,48)=12.56, p=.001, ηp2
=.207, but Group*Measurement interaction was not significant. Group factor differences only pointed out significant improvement in the tDCS‐NeuronUP group compared to the Sham‐Videogame group.

Prospective memory (Figure 2) also showed improvement in post‐intervention, F(1,48)=12.79, p=.001, ηp2
=.210, but neither main Group effect or Group*Measurement interaction achieved significance.

Conclusions

Trends showed significant memory improvements particularly in NeuronUP‐groups. tDCS seems to take some responsibility in the improvement mainly in the videogame‐group. The intensity of training and automatic difficulty adjustment associated with the NeuronUP app, along with the enhancing effect of tDCS, appear to be responsible for further improving memory.
FANTASTIC‐D: A lifestyle questionnaire for people with dementia living at home
Authors: Schüssler Sandra , Zuschnegg Julia , Schatz Manuela , Russegger Silvia , Paletta Lucas , Draxler Sandra , Koini Marisa , Steiner Josef , Zweytik Elke , Ploder Karin , Strobl Bernhard , Hofmarcher‐Holzhacker Maria
Published: February 2022

Background

The neglect of certain lifestyle factors entails a risk for negative outcomes (e.g., reduced quality of life, cardiovascular diseases, increased mortality) for people with dementia. Internationally, short overview instruments for identifying lifestyle risk factors in people with dementia to positively influence the course of the disease are lacking. The FANTASTIC questionnaire, originally developed in Canada, provides a short but comprehensive assessment of physical and psychosocial lifestyle risk factors. The aim of this study was to translate the FANTASTIC lifestyle questionnaire into German, to adapt it for people with dementia and to pretest the questionnaire regarding completeness, comprehensibility and face validity.

Method

In accordance with the principles of the ISPOR society, the literature and expert knowledge, the FANTASTIC questionnaire was forward‐backward‐translated, adapted to people with dementia and checked by means of two pre‐tests (expert review, cognitive interviews). Three experts participated in the expert review (including three members of the research team) and gave feedback on the retranslated questionnaire, ensuring face validity. Cognitive individual interviews were then conducted with five people with mild dementia living at home. A qualitative content analysis was performed using a concept‐driven coding frame.

Result

Evaluation of the expert review resulted in the following changes: usage of question words, addition of synonyms/examples for better understanding, development of a new dementia‐specific domain, and creation of answer cards (A4 landscape format) to make data collection easier for people with dementia. Analysis of cognitive interviews showed that people with dementia had problems with certain terms in the questions (e.g., emotional support), and with individual answer options (e.g., not weekly). The incomprehensible terms were either replaced by more understandable synonyms (e.g., "mental support" instead of "emotional support") or were explained with additional synonyms/examples in brackets after the questions. Unclear answer options were made more explicit (e.g., "1‐3 times per month" instead of "not weekly"). Furthermore, an interviewer manual was developed.

Conclusion

The FANTASTIC‐D is now available to assess lifestyle risk factors for German‐speaking people with dementia living at home. The next step in the study will be to test further psychometric properties and to establish the English version of FANTASTIC‐D.
Thalamic abnormalities in older adults with early‐onset depression using structural magnetic resonance imaging
Authors: Espinosa Nicole , Duffy Shantel L , LaMonica Haley , Mowszowski Loren , Hickie Ian B , Palmer Jake R , McKinnon Andrew C , Naismith Sharon L
Published: February 2022

Background

The thalamus is a key diencephalic structure involved in major depressive disorder (MDD). In particular, studies have consistently revealed abnormalities in thalamic volumes in older adults with late‐onset depression (LOD). However, similar abnormalities in older adults with early‐onset depression (EOD) have not been well studied.

Method

Fifty‐nine euthymic participants with a history of EOD and fifty‐nine matched comparison participants without a lifetime history of depression underwent neuroimaging, medical and neuropsychological assessments. Thalamic volumes were compared between groups. Due to the right hemispheric (RH) dominance theory of MDD, we explored both bilateral and right hemispheric thalamic volumes. Multiple regression analyses were used to evaluate between‐group and within‐group effects. A correlational analysis examined associations between group and cognitive performance.

Result

Relative to the comparison group, those with EOD had significantly larger bilateral and RH thalamic volumes. Those with EOD, those who were younger, and those who had fewer years of education, demonstrated larger bilateral thalamic volumes. When split by group (EOD vs comparison group), only age remained significantly different for those with EOD. For RH volumes, those with EOD and those who were younger demonstrated larger RH thalamic volumes. When split by group, the results showed that age only was significant for both groups. No significant correlations were found between cognitive performance and EOD groups.

Conclusion

Older adults with a history of EOD showed significantly larger bilateral and RH thalamic volumes. Further research is needed to further elucidate the underlying mechanism of this change.
Stepwise connectivity paves the way to reveal functional network vulnerability in age‐related neurodegenerative disorders
Authors: Basaia Silvia , Agosta Federica , Cividini Camilla , Spinelli Edoardo Gioele , Castelnovo Veronica , Leocadi Michela , Calderaro Davide , Canu Elisa , Filippi Massimo
Published: February 2022

Background

Ageing is the main risk factor for most neurodegenerative diseases and results in complex transformations of the human brain function. The aim of this study was to investigate how topological organization of the brain connectome changes with age using resting‐state functional MRI and stepwise functional connectivity (SFC) analyses.

Method

138 controls were recruited and divided into two groups according to age: 55 young (20‐30 years [YC]) and 83 old (41‐84 years [OC]). SFC analysis aims to characterize regions that connect to specific seed brain areas at different levels of link‐step distances. Eight well‐known hubs of the human connectome were selected as seeds: middle frontal gyrus, rostral anterior and posterior cingulate cortex, precuneus, inferior parietal, middle temporal and lingual gyri and pericalcarine cortex. Whole‐brain two‐sample t‐test comparisons between groups were performed.

Result

At one‐link step distance, in OC, all the seed regions displayed decreased regional–local functional connectivity with superior frontal and medial orbital frontal gyri, rostral anterior and isthmus cingulate cortex, precuneus and middle and inferior temporal gyri relative to YC; across intermediate link‐steps, a reduced connectivity was observed between all seed regions and frontal‐parietal lobes. By contrast, at the first link‐step distance, YC showed lower connectivity only between few seed regions and precentral, paracentral and lateral occipital gyri compared to OC. At intermediate link‐step distances, increased connectivity with sensorimotor regions was found in OC relative to YC.

Conclusion

SFC approach might have important implication providing a starting point for evaluating network disruptions in age‐related neurodegenerative disorders. European Research Council (StG‐2016_714388_NeuroTRACK).
Taurine and N‐acetylcysteine supplementation prevents memory impairment in high‐fat diet‐fed female mice
Authors: Garcia‐Serrano Alba M. , Duarte Joao M.N.
Published: February 2022

Background

The risk to develop memory impairment in has been widely investigated in type 2 diabetes (T2D). There are several mechanisms proposed for T2D‐associated cognitive impairment, such as brain insulin resistance, synaptic dysfunction, inflammation, gliosis, or disruption of neuron‐astrocyte interactions (Garcia‐Serrano & Duarte, 2020). On the other hand, supplementation with the antioxidants taurine and N‐acetylcysteine (NAC) have been suggested to have benefits on reducing T2D phenotype and enhancing memory performance in diabetic mice models (Inam‐U‐Ilah et al, 2018). We aimed at studying mechanisms by which taurine and NAC improve memory in obesity‐associated T2D.

Method

Ten‐week‐old female C57Bl/6J mice were divided in 6 groups (n=10): control diet (CD 10%‐fat diet), high‐fat diet (HFD; 60% fat diet), CD/HFD supplemented with 3% taurine in drinking water (CD+T or HFD+T) or 3% N‐acetylcysteine (CD+NAC or HFD+NAC). After 2 months, hippocampal metabolic profiles were analysed by magnetic resonance spectroscopy (MRS) under isoflurane anaesthesia, memory performance was evaluated by behavioural testing with the novel location recognition (NLR) and novel object recognition (NOR) tasks, and diabetes phenotype was measured by monitoring weight, glucose tolerance test and HOMA insulin resistance.

Result

HFD group was overweight compared to CD group (p<0.01), with no effects of taurine or NAC. HFD‐fed mice showed glucose intolerance compared to CD mice (p<0.001). Although HFD+T and HFD+NAC groups were glucose intolerant but to a lesser degree than untreated HFD mice (p< 0.05 and p<0.01, respectively). None of the experimental groups displayed insulin resistance, neither memory impairment in the NOR test. The NLR test showed memory impairment in the HFD‐fed mice compared to controls (p<0.037), which was prevented by taurine and NAC treatments. The metabolic profile showed decreased concentration of the neuronal marker N‐acetylaspartate and lactate in the hippocampus of HFD‐fed mice compared to controls (p<0.01). While N‐acetylaspartate concentrations were recovered to control levels in both HFD+T and HFD+NAC mice, only HFD+NAC group recovered lactate concentration in the hippocampus.

Conclusion

Memory impairment in HFD‐fed mice was restored by taurine and NAC treatments, through mechanisms that involve metabolism in mitochondria, which is the organelle responsible for producing N‐acetylaspartate in neurons.

Garcia‐Serrano & Duarte, 2020. https://doi.org/10.1177/0271678X20942397

Inam‐U‐Ilah et al, 2018. https://doi.org/10.1007/s00726‐018‐2544‐4
The Caribbean‐American Dementia and Aging Study (CADAS): A multinational initiative to address dementia in Caribbean populations
Authors: Llibre‐Guerra Jorge J , Li Jing , Harrati Amal , Jiménez‐Velazquez Ivonne , Acosta Daisy M , Llibre‐Rodriguez Juan J , Liu Mao‐Mei , Dow William H
Published: February 2022

Background

Latinos represent the fastest growing proportion of dementia cases among different ethnic groups. Most of the studies in Alzheimer’s Disease (AD) include Latino populations within the same group, failing to sufficiently account for the real richness of linguistic, ethnic, ancestry, cultural, and socioeconomic diversity represented across Latino communities (e.g., Caribbean‐Hispanic vs Non Caribbean‐Hispanics), yet there is substantial AD disparities and disease heterogeneity among Hispanic groups.

Methods

The Caribbean‐American Dementia and Aging Study (CADAS) is a multinational initiative aimed to answer key questions regarding dementia determinants and consequences in Caribbean‐origin populations in origin communities as well as among emigrant populations in the United States. By building a collaborative team of leading Caribbean and U.S‐based dementia researches, CADAS will analyze differences in dementia prevalence and risk factor profiles between Caribbean‐Hispanics living in the main Hispanic Caribbean Islands and extend comparisons to Hispanic immigrant groups in the US as well as non‐Hispanic whites, exploiting the considerable difference in life course risk exposures across these populations.

Results

Preliminary findings from the CADAS study indicate that prevalence of dementia in the older Caribbean population is high, both in the main islands and in U.S. compared to non‐Hispanic‐whites. We found overall weaker associations between education and dementia probability in the three main Caribbean islands. By contrast, a stronger association between education and dementia probability was found in the US among non‐Hispanic whites, Mexican Hispanics, and non‐Mexican Hispanics; these persist even after controlling for income and wealth.

Conclusions

There are differential associations between SES risk factors, education, and dementia probability between Caribbean islands and the U.S., which may be attributed to differences across societies in risk factors correlated with education. The CADAS study will fill a critical gap in AD knowledge, exploiting rich variation in life‐course exposures to better disentangle genetic versus environmental determinants of dementia levels and disparities. Future studies within this populations will focus on early‐life socioeconomic status, gene by environment interactions and societal cost.
Outcomes valued by people living with dementia and their carers: A qualitative systematic review with a qualitative synthesis
Authors: Booi Laura , Wheatley Alison , Brunskill Greta , Banerjee Sube , Manthorpe Jill , Robinson Louise , Bamford Claire
Published: February 2022

Background

Growing numbers of interventions are being developed to support families living with dementia, but the extent to which they address the issues of most importance to people living with dementia and their carers is unclear. The aim of this review is to synthesise the best available qualitative evidence on the outcomes valued by (a) people living with dementia and (b) their carers, both for themselves and each other. This review is a part of a wider project aiming to improve post diagnostic support for people living with dementia and their carers.

Method

We will use thematic synthesis methodology. Studies from 1990 onwards will be eligible if they include qualitative data on the views of people living with dementia or their carers on valued outcomes or the lived experience of dementia. Databases to be searched include MEDLINE, CINAHL, PsycInfo and Social Sciences Premium Collection, in addition to systematically gathered grey literature. Rayyan QCRI software will be used to manage the screening processes and NVivo software will be used to manage data extraction and analysis. The review will also critically evaluate the extent to which international recommendations address the areas of importance to people living with dementia and their families.

Results

The results of this review will be presented at the conference.

Conclusion

The findings will be of relevance to researchers, policy makers, and providers and commissioners of dementia services.
Alzheimer's disease detection using explainable AI on PET images
Authors: Weatheritt Jack , Palombit Alessandro , Manber Richard , Wolz Robin
Published: February 2022

Background

Automated detection of Alzheimer’s disease features from imaging is a widely worked on machine learning problem, facilitated by the amount of data available through programs such as ADNI. Consequently, “black‐box” neural networks are starting to become viable and accurate approaches to patient classification. However, such methods are typically opaque, and their results are difficult to interpret – limiting their deployment in clinical trials.

Our aim through this work is to apply recent advances in explainable deep neural networks and show that our model is indeed sensitive to the underlying metabolic processes. This makes the deep learning prediction process more transparent.

Method

We use 520 AC‐PC aligned [18F]‐FDG‐PET scans from the ADNI cohort from AD and healthy control (CG) groups. These are then fed to a deep neural network (ResNet, 3.4 million parameters), which learns to classify each scan. We then validate predictive capabilities of the model on 120 previously unseen scans.

Using the validation data, we also calculate a saliency map for each scan. The map represents regions that were important for the model’s prediction. For each layer of the neural network, we calculate a cross‐entropy like quantity amongst the activations for a given layer. A group‐wise value is then calculated by averaging the subject maps within each group. The resulting difference highlights which voxels are activated during AD/CG classification. Principal component analysis reveals the regions of spatial location highest variance in the activations.

Result

The algorithm scored a mean accuracy of 89.2%. This is comparable with other approaches in the literature. Average saliency maps and their 2nd principal component can be seen in figures 1, 2 and 3.

Conclusion

The algorithm is shown to accurately distinguish between AD and CG. By using the tools outlined above, we probe how the model arrives at those conclusions. The directions of maximal variance in the saliency maps shows the importance of the precuneus and hippocampi (increased saliency magnitude). This is corroborated by the difference in the mean CG and AD maps. These regions are known areas of FDG hypometabolism – a result previously identified and available in the literature.
Use of amyloid PET scans in the clinical management of patients with cognitive decline in a naturalistic setting at a tertiary memory disorders clinic
Authors: Vives‐Rodriguez Ana , Wang Ryan , Schiloski Kylie A. , Hajos Gabor P. , Turk Katherine W. , Budson Andrew
Published: February 2022

Background

Amyloid PET(aPET) is used to aid differential diagnosis, increase diagnostic confidence and assist with management of patients with cognitive decline. In the United States, aPETs are not often used because they are costly and not covered by insurance. VA Boston Healthcare System provides a unique opportunity where aPETs are available for clinical purposes and are ordered to assist in the differential diagnosis of patients with cognitive decline when clinically relevant. This study aims to determine which factors are associated with the use of aPET for diagnostic confirmation of AD in a naturalistic setting at a tertiary memory disorders clinic and to determine which factors predict an abnormal result.

Method

We conducted a retrospective review of all patients that were evaluated for cognitive decline at the Memory Disorders Clinic at Boston VA Medical Center from 9/2016 to 1/2020. Clinical information was extracted, including demographics, neuropsychological testing, and imaging studies. We compared patients' characteristics for whom an aPET was ordered and those for who a diagnosis was made without an aPET. We reviewed the characteristics of patients with positive vs. negative aPET

Result

565 patients were evaluated. 202 patients (35.75%) had an aPET as part of their workup; of these, 72 patients (36.5%) had an abnormal result. Factors associated with clinicians ordering the aPET were: younger age, longer clinical course, absence of amyloid angiopathy on MRI, and a diagnosis of mild cognitive impairment (MCI) and mild dementia. When performing multivariate analysis of the clinical characteristics, imaging, and neuropsychological tests of patients, only a positive family history of dementia (p=0.004) and presence of false‐positives on recognition in the CERAD list learning task (p=0.004) were associated with an abnormal result.

Conclusion

In this cohort, aPETs were ordered in younger patients who fulfilled the criteria for MCI and mild dementia, and had a longer clinical course. Only a family history of dementia and false‐positives on recognition during a list learning task were significantly associated with an abnormal result. The results of this study may be informative both regarding how aPET may be used if covered by insurance and regarding clues to determining underlying Alzheimer’s pathology without biomarkers.