Western University

Objective assessments of shoulder motion are paramount for effective rehabilitation and evaluation of surgical outcomes. Inertial Measurement Units (IMU) have demonstrated promise in providing unbiased movement data. This study is dedicated to evaluating the concurrent construct validity and accuracy of a wearable IMU-based sensor system, called ‘Motion Shirt’, for the assessment of humero-thoracic motion arcs in patients awaiting shoulder replacement surgery. This evaluation was conducted by comparing Motion Shirt data with the Dartfish Motion Analyzer software during the Functional Impairment Test-Hand and Neck/Shoulder/Arm (FIT-HaNSA) test. Thirteen patients (age > 50), who were awaiting shoulder replacement surgery, were recruited. The Motion Shirt was employed to measure angular humero-thoracic movements in two planes during the FIT-HaNSA test. Simultaneously, two cameras recorded the participants’ movements to provide reference data. Bland-Altman plots were generated to visualize agreement between the Motion Shirt and the reference data obtained from the Dartfish Motion Analyzer software. The data analysis on Bland-Altman plots revealed a substantial level of agreement between the Motion Shirt and Dartfish analysis in measuring humero-thoracic motion. In Task-1, no significant systematic errors were exhibited, with only 3.27% and 2.18% of points exceeding the limits of agreement (LOA) in both elevation and the Plane of Elevation (POE), signifying a high level of concordance. In Task-2, a high level of agreement was also observed in Elevation, with only 3.8% of points exceeding the LOA. However, 5.98% of points exceeded LOA in POE for Task-2. In Task-3, focused on sustained overhead activity, the Motion Shirt showed strong agreement with Dartfish in Elevation (2.44% points exceeded LOA), but in POE, 7.32% points exceeded LOA. The Motion Shirt demonstrated a robust concordance with Dartfish Motion Analyzer system in assessing humerothoracic motion during the FIT-HaNSA test. These results affirm the Motion Shirt’s suitability for objective motion analysis in patients awaiting shoulder replacement surgery.

Purpose The SARS-CoV-2 vaccination has reduced COVID-19 infection, though facial nerve palsy (FNP) has emerged as a notable side effect of the vaccine. We evaluated the current literature on the clinical presentation and outcomes of FNP related to COVID-19 vaccination. Methods A comprehensive search of seven databases was conducted for studies up to January 2023. We included individually reported patients on FNP following COVID-19 vaccination, while cases with co-existing neurological disorders or secondary causes of FNP were excluded. Pooled descriptive and inferential analyses were conducted, with prognostic factors evaluated through regression and Kaplan–Meier survival analysis. Results A total of 33 studies were included, with data from 52 patients who developed post-COVID-19 vaccination FNP (PV-FNP). Most cases (71%) followed mRNA vaccines, primarily occurring after the first dose and within the first week post-vaccination. Nearly all cases (98%) were unilateral, with Grade III palsy being most common. Complete recovery was achieved in 55% of patients, significantly lower than pre-pandemic rate (83%). A longer latency period was associated with a reduced likelihood of full recovery, and females experienced faster recovery compared to males. Conclusion FNP following SARS-CoV-2 vaccination tends to present as mild and unilateral, with a lower full recovery rate compared to pre-pandemic cases. Symptoms often develop within the first week after vaccination, and earlier symptom onset is associated with a higher likelihood of full recovery. Recognizing these patterns provides valuable guidance for clinicians in counseling patients about prognosis and managing follow-up care effectively.

Fossil-free ironmaking is crucial in mitigating CO2 emissions within the iron and steel industry. Among the various solutions being explored, hydrogen-based direct reduction stands out as one of the most promising approaches for sustainable ironmaking, offering significant potential for medium-term implementation. This study examines the use of pure hydrogen in the direct reduction of industrial iron ore pellets, focusing on the effects of temperature (700–1000 °C) on the reduction kinetics and microstructural evolution. Utilizing a custom-made thermogravimetric setup and microscopic analysis, the research characterizes the reduction process through continuous weight measurements and provides detailed insights into the microstructural and compositional changes across various pellet regions. Through detailed microscopic examination at various stages of reduction, the study emphasizes the heterogeneous nature of the process, particularly within the core of the pellets where complete metallization proves challenging at lower temperatures. The reduction rate was found to be highly dependent on both the temperature and the initial microstructure of the iron ore pellets, as well as its evolution during the reduction process.

Background Commonly used screening measures of cognitive function such as the Montreal Cognitive Assessment (MoCA) are not sensitive to assess cognitive function among individuals with severe cognitive impairment due to floor effect. The Severe Cognitive Impairment Rating Scale (SCIRS) was designed to assess cognitive function in those with severe cognitive impairment, however, psychometric properties of its English version have not been reported. Method Using the existing data from StaN and tTED studies, floor and ceiling effects (percentage of minimal or maximal scores) of SCIRS and MoCA were examined, and the association between SCIRS and MoCA was evaluated. Result Data from 141 participants (mean age = 78.7, 56% females) who completed either the SCIRS (n = 122) or MoCA (n = 80) were collected (n = 61 completed both). There was robust association between SCIRS and MoCA, supporting criterion validity of the SCIRS as a measure of cognitive function. SCIRS had a lower floor effect (13.1% minimal scores) as compared to the MoCA (27.5% minimal scores). Out of 22 participants with minimal scores on the MoCA, 16 participants completed the SCIRS with mean score of 9.8 (SD = 7.5). Conclusion SCIRS appears to be a valid measure of cognitive function, showing better variance among individuals with severe cognitive impairment, as compared to MoCA.

Background Primary progressive aphasia (PPA) is a dementia syndrome characterized by language and communication impairments, with relative sparing of other cognitive domains. As a relatively rare dementia syndrome, there are few measures developed and validated for individuals with PPA. Development of outcome measures tailored to the communication experiences of persons with PPA (PwPPA) is critical for the accurate assessment of interventions success. The 10‐item Communicative Participation Item Bank (CPIB) has been used as a measure for communication participation in PPA. However, the CPIB was validated as a disorder‐agnostic measure and its content validity for PPA has not been evaluated. This study aims to evaluate the face and content validity of the 10‐item CPIB for PwPPA and their communication partners (CP). Method Cognitive interviews were conducted with participants (N = 12) who had previously completed the CPIB during the Communication Bridge 2 randomized controlled trial (NCT03371706) and with four participants unfamiliar with the CPIB. PwPPAs and CPs completed the CPIB during a semi‐structured interview assessing measure format, instructions, response options, item comprehension, and item relevance. To evaluate content validity, participants were asked open‐ended questions to elicit relevant communication participation experiences missing from the questionnaire. Closed‐ended responses (e.g., clarity, relevance) were tabulated, and open‐ended responses (e.g., item comprehension, missing content) were thematically analyzed. Summaries of measure format, instructions, and response options were generated, as well as item‐level findings regarding comprehension, relevance, and missing content. Result Both PwPPAs and CPs: a) considered the instructions to be clear (n = 16, 100%); b) recommended adding a fifth response option (e.g., “Somewhat; n = 11) to better represent the range of communication situations; c) reported all items except one (“persuade…to see a different point of view”) were relevant (n≥13; ≥81%, for 9 items); and d) talking on the phone was the most reported missing communicative participation situation (n = 12; 75%). Further, 3 participants reported talking over videochat, and 4 participants reported email/texting as missing. Results were similar between CPIB‐experienced and CPIB‐naïve participants. Conclusion Findings indicate that modifications to the 10‐item CPIB short form may be needed for use with PwPPA and their CPs to more fulsomely capture communication participation in PPA.

Background Primary progressive aphasia (PPA) is a currently incurable and relatively rare language‐based neurodegenerative dementia syndrome, which negatively impacts communication and quality of life. Non‐pharmacologic interventions show promise but have lacked randomized controlled trials (RCT). Here we report outcomes for Communication Bridge‐2 (CB2), the first global telemedicine speech‐language (RCT) for PPA. Method CB2 is an international, single enrollment site, Phase 2, Stage 2, parallel‐group, active control, behavioral RCT delivered via video‐chat to individuals with PPA and their communication partners. CB2 is supported by a custom web application. Participants were randomized 3:2 into one of two arms: Communication Bridge™ a dyadic intervention based on communication participation models, or, the Control intervention, a non‐dyadic intervention based on impairment models. Participants completed two intervention blocks over ∼12 months. Primary outcomes included communication confidence and participation measures assessed at baseline, each intervention block, and ∼12 months post‐enrollment. Other outcomes included word and script performance. Post‐study interviews captured participant experiences and informed feasibility. Result Ninety‐five PPA participant dyads (mean enrollment age of PPA participants: 67.1 years, 49% female) were randomized (n = 4 countries). Dropout was <10%. Procedural and documentation fidelity were high (>90%, for both). Theoretical fidelity showed strong within‐arm alignment. Experimental arm superiority was demonstrated at Block 1 for the Goal Attainment Scale, measurement, a primary participation outcome evaluated by a blinded clinician. The Communicative Participation Item Bank showed positive within‐group responsiveness at Block 1 exclusively for the experimental arm. Communication confidence measurement was less responsive. Other outcomes including word and script training, showed significant gains at Block 1 for both groups. Post‐study interviews suggested high feasibility. Conclusion Results suggest feasibility and initial efficacy for a global telemedicine intervention, providing an exciting path for implementation and dissemination of clinically meaningful interventions for Alzheimer’s and related dementias using telehealth models that can improve care access.

Background The relevance of a plasma membrane Na⁺‐Ca²⁺ exchanger isoform‐3 protein, NCX3, is widely evidenced in neuronal physiology. However, the mechanisms leading to NCX3 expression deficits in Alzheimer’s disease (AD) pathology and its value as a target in AD pharmacological medicine remain incomplete. Methods Inhibition and rescue experiments were performed in cultured primary neurons of 5×FAD mice model of AD using pathological Aβ1‐42 isolated from a conditioned medium of BHK cells, a cell line which does not constitutively express NCX3, stably transfected with a plasmid expressing human wild type Aβ1‐42. Results Pathological forms of Aβ1‐42 interfere with NCX3 expression level and neuronal viability. Pronounced expression levels of NCX3 and state of endurance were observed in the control group compared with those treated with pathological Aβ1‐42. Conclusion NCX3 merits in‐depth study consideration as a predictive biomarker and in developing a potential novel pharmaceutical intervention method for AD. Keywords: Alzheimer’s disease, Aβ1‐42, Na⁺‐Ca²⁺ exchanger isoform‐3

Background Type 2 diabetes (T2D) and older age are well‐known risk factors for dementia. Indeed, there is evidence that older adults not diagnosed, but at‐risk for T2D can show early signs of cognitive decline, further exacerbated by excessive body weight or high blood glucose levels. Such a finding would have implications for early treatment strategies; however, the evidence is still sparse. We examined the correlation of risk factors for diabetes with cognitive function in older adults at‐risk for T2D using a battery of touchscreen tasks translated from their rodent versions, as well as traditional pen‐to‐paper cognitive tests. Method Sixty‐five older adults (69.39 ± 10.31 years old, 68% female) at‐risk for T2D (BMI = 25 kg/m2, hemoglobin A1c = 6.0%, CANRISK score = 21) completed 3 novel touchscreen tasks: paired associative learning (PAL) (learning and object‐in‐location memory), progressive ratio (motivation), and trial unique, non‐matching to location (TUNL) (spatial pattern separation and working memory). They were also tested on pen‐to‐paper cognitive tests: trail‐making (task switching), Stroop (selective inhibition), and digit span (working memory). A correlation analysis was performed between BMI or HbA1c and cognitive performance. Performance on touchscreen tasks was analyzed using a repeated measures one‐way ANOVA. Result Higher HbA1c levels were correlated with lower digit span scores (r2 = 0.12, p = 0.011). There was no correlation between breakpoint (motivation level) and BMI or HbA1c during the progressive ratio task (r2 = 0.0, p = 0.38). Interestingly, this population performed at chance level (59.7 ± 5.3% accuracy) on the PAL task, indicating they were unable to learn object‐location paired associates. When manipulating the spatial similarity in distance between stimuli during the TUNL task, older adults at risk for diabetes were 10% lower in accuracy when stimuli were close together compared to further apart (p<0001). Participants also responded more slowly to stimuli at choice during the TUNL task during the heaviest working memory load condition (p = 0.003). Conclusion Older adults at‐risk for T2D exhibit decreased performance on tasks with higher demands on spatial and working memory. Future research will compare performance on all tasks to healthy age‐matched controls and reassess performance after a six‐month exercise intervention.

Background Polyunsaturated fatty acids are metabolized by cytochrome P450 (CYP450) into anti‐inflammatory, pro‐resolving epoxides, which are rapidly converted to inactive and cytotoxic diols by soluble epoxide hydrolase (sEH). Increased CYP450‐sEH metabolites are associated with worse cognition in type 2 diabetes mellitus (T2DM), and greater white matter hyperintensities (WMH) in patients with stroke. We examined whether the relationship between linoleic acid (LA)‐derived CYP450‐sEH metabolites (oxylipins) and small vessel disease (SVD) markers differ across diabetes status. Method Cognitively impaired patients with neurodegenerative/ vascular cognitive disorders from the Ontario Neurodegenerative Disease Research Initiative (https://braininstitute.ca/ondri) were classified as having normoglycemia, prediabetes, or T2DM based on a self‐report of diabetes diagnosis, glycated hemoglobin (HbA1c), and antidiabetic medication use. Unesterified plasma oxylipins were quantified via ultra‐high‐performance liquid chromatography tandem mass spectrometry, from which diol to epoxide ratios, a proxy of sEH activity, were calculated. SVD markers included WMH, perivascular spaces (PVS), and lacunes (LACN) quantified through T1‐ and T2‐weighted structural MRI. Linear regression models controlling for age, sex, BMI, intracranial volume, hypertension, APOE‐ε4 status, HDL, HbA1c, neurodegenerative diagnoses, and antidiabetic medication use, were used. Result Among 493 participants, 238 normoglycemic (48.4% female, age = 67.6±8.5 years), 161 prediabetes (35.4% female, age = 69.8±6.8 years), and 94 T2DM participants (20.2% female, age = 69.5±7.2 years) were identified. In the whole group, increased 9,10‐LA ratio was associated with greater PVS (β = 0.097, p = 0.030), but not WMH or LACN. No association was observed with the 12,13‐LA ratio. Significant interaction with HbA1c predicting WMH was observed with the 9,10‐LA ratio (β = 0.530, p = 0.020), and similar effect size was seen with the 12,13‐LA ratio (β = 0.482, p = 0.069). Subgroup analyses revealed a positive association in T2DM only (9,10‐LA: β = 0.313, p = 0.001; 12,13‐LA: β = 0.226, p = 0.020). No interaction effects with HbA1c predicting PVS or LACN were observed. In the normoglycemic subgroup, the 12,13‐LA ratio was negatively associated with LACN (β = ‐0.121, p = 0.025), whereas in T2DM, a positive association was observed (β = 0.213, p = 0.039). Similarly with the 9,10‐LA ratio, in the normoglycemic subgroup, a non‐significant negative association was observed (β = ‐0.100, p = 0.071), whereas in T2DM, a positive association was observed (β = 0.225, p = 0.032). Conclusion Diabetes status affects the association between LA‐derived oxylipins and SVD markers. sEH may be a potential therapeutic target in T2DM to reduce neurovascular damage and subsequent cognitive decline.

Background Parkinson’s disease is a progressive neurodegenerative disorder that is becoming more prevalent as the population ages. Mobile neuroimaging has made it possible to observe cortical activity in this population outside of standard laboratory environments. Yet, few studies have explored the portability of these devices in a true real‐world environment without a specific task imposed on participants (e.g., dual task, motor demands). Method Mobile electroencephalography (EEG) was utilized to examine and compare cortical activity during sitting in different environments across older adults with and without Parkinson’s disease. We used the Muse S Generation 2 Brain‐Sensing Headband to record brain function. The first condition involved participants sitting in a standard laboratory environment while their brain activity was recorded. In the second condition, participants sat in an indoor space that included a living green wall, natural light, and other people while their brain activity was recorded. Fast Fournier Transform (FFT) analysis was performed on the raw EEG data to obtain corresponding waves for each electrode to examine power (uV^2) at each frequency (Hz). Result Preliminary findings demonstrate significant differences in mean cortical activations across older adults with and without Parkinson’s disease. Differences in cortical activations were also observed when comparing the laboratory and real‐world environment. Conclusion These findings suggest that elicited brain activity may differ across older adults with and without Parkinson’s disease and across different environments. These findings expand current knowledge on Parkinson’s disease, brain function, and cognition using real‐world methods and technology, which may inform interventions to increase quality of life among this population. As our findings suggest that environmental factors may modulate cortical activity, we also highlight the potential and importance for real‐world methods to supplement standard research practices to increase the ecological validity of studies conducted across the scientific community.

Background Community engaged research (CER) has been critical for increasing diversity in Alzheimer’s studies. However, the effectiveness of CER for engaging a diverse population of ‘SuperAgers,’ has been largely unstudied. SuperAgers are individuals age 80+ with superior episodic memory. The multi‐site SuperAging Research Initiative (SRI) seeks to recruit at least 500 SuperAgers and similarly aged controls, including 40% who identify as Black. This report summarizes initial CER strategies, implementation of new strategies, and enrollment success across the first ∼18 months. Method Semi‐structured interviews were conducted at each site to assess current CER strategies and perceptions of facilitators/barriers to CER approaches. Interviews were transcribed and concept mapping was used to identify key themes across sites. Key themes are reported here along with recruitment outcomes across the sites over the first ∼18 months. Initial responsive actions are described. Result SRI sites were selected based on their historical success engaging and recruiting Black older adults in cognitive aging research; however, identification and recruitment of SuperAgers was new for most sites. Results revealed strong current community engagement practices across sites. Emergent themes included prioritizing diverse staff, barriers to CER, strengths of the multi‐site design, the value of research to participants. Sites also implemented several CER strategies including building/enhancing community partnerships, providing community presentations, and engaging community members and enrolled participants in feedback sessions related to recruitment methods. Responsive actions of the SRI included development of participant informed culturally tailored recruitment flyers, videos, and photos, which incorporated site‐level feedback. Holiday‐themed appreciation gifts were provided to enrolled participants. Initial enrollment included 173 participants (mean age: 86.6 years). Diverse recruitment across sites ranged from 0‐27%. Diverse recruitment increased over the second half of the year, potentially suggesting early success with CER strategies. Conclusion Initial recruitment reflects a starting point for the enrollment of Black SuperAgers and Controls. Future plans involve implementing additional study‐wide CER recruitment methods, utilizing online registries as a recruitment source, and establishing ambassador boards to boost SRI enrollment of older Black adults. Strategy success will be carefully quantified, and outcomes will be shared for future research use.

Background People with mild cognitive impairment are at greater risk of Alzheimer’s disease. Physical activity (PA), sedentary behaviour, and sleep are movement behaviours constituting the 24‐hour activity cycle (24‐HAC) and are interactively associated with cognitive and brain health. However, the relationship between 24‐HAC compositions (i.e., time in one behaviour relative to remaining) and brain volume in this population remains underexplored. We aimed to investigate the associations between 24‐HAC compositions and time reallocation of 24‐HAC movement behaviours with brain volume. Method A cross‐sectional study in 110 community‐dwelling adults (55+ years) with mild cognitive impairment (Montreal Cognitive Assessment <26/30). MotionWatch8© assessed 24‐HAC movement behaviours (5‐7 days). Compositional data analysis determined 24‐HAC compositions (four isometric log‐ratio pivot coordinates). FreeSurfer quantified gray matter volume using T1‐weighted magnetic resonance imaging. Linear regressions adjusted for age, sex, intracranial volume, and education determined 24‐HAC compositions and brain volume associations. Compositional isotemporal substitution analysis estimated the difference in brain volume associated with reallocating time between pairs of 24‐HAC movement behaviours. The Benjamini‐Hochberg false‐discovery rate (FDR) adjusted p‐values for multiple comparisons. Result Higher moderate‐to‐vigorous PA composition was associated with greater cortical volume in the inferior temporal gyrus TE2a region (ß = 0.30, 95% CI = 0.15; 0.44, FDR‐adjusted‐p = 0.030). Higher light PA composition was associated with lower cortical volume in the TE2a region (ß = ‐0.45, 95% CI = ‐0.65; ‐0.24, FDR‐adjusted‐p = 0.015). Sedentary behaviour and sleep were not associated with brain volume (FDR‐adjusted‐p>0.05). Reallocating 30 minutes from sedentary behaviour to moderate‐to‐vigorous PA was associated with 2.1% greater volume in the TE2a region (ß = 0.06, 95% CI = 0.02; 0.10, p<0.001). Reallocating 30 minutes from moderate‐to‐vigorous PA to sedentary behaviour was associated with 2.8% lower volume in the TE2a region (ß = ‐0.08, 95% CI = ‐0.14; ‐0.02, p<0.001). Conclusion Greater light PA composition may happen at the expense of lower moderate‐to‐vigorous PA composition, which could explain its associations with lower cortical volume. Greater moderate‐to‐vigorous PA composition and reallocating time from sedentary behaviour to moderate‐to‐vigorous PA may counteract cortical atrophy in an Alzheimer’s disease signature region in people with mild cognitive impairment.

Background The optimal combinations of modifiable risk factors to be targeted in preventive dementia trials may vary across countries and settings. We aimed to identify the combinations of modifiable risk factors associated with cognitive change in Canadian adults. Method Population Attributable Fraction analyses on 30,097 participants from the Canadian Longitudinal Study on Aging and prevalence of 2, 3 and 4 risk combinations of the 12 modifiable risk factors identified in the 2020 Dementia Lancet report were estimated to note the ten most prevalent combinations. Association between the identified combinations and 3‐year cognitive changes was examined with linear mixed models. Result Risk factor combinations were associated with greater change in memory than executive function (Table 1). Among the ten most prevalent dyad combinations, hearing loss and physical inactivity showed the largest adjusted effect on global cognition (β = ‐0.08, 95% CI ‐0.09 to ‐0.06), memory (β = ‐0.1, ‐0.18 to ‐0.14), and executive function (β = ‐0.03, ‐0.04 to ‐0.02). The triad of hearing loss, physical inactivity, and sleep disturbance was associated with the largest adjusted effect across all domains (global: β = ‐0.06, ‐0.07 to ‐0.04; memory: β = ‐0.12, ‐0.15 to ‐0.09; Executive Function: β = ‐0.03, ‐0.04 to ‐0.01). The tetrad of hearing loss, depression, physical inactivity, and sleep disturbance was associated with the largest adjusted effect on memory (β = ‐0.11; ‐0.18 to ‐0.05). The dyad that was associated with greater memory change than their individual effect was hearing loss and physical inactivity, while it was depression, physical inactivity, and sleep disturbance for the triad combination (Figure 1). The tetrad combination included obesity, depression, physical inactivity, and sleep disturbance. Conclusion Identifying risk factor clusters with the highest prevalence and potential effect size can optimize efficiency of trial design. Intervention programs should consider including hearing loss and physical inactivity or obesity, depression, physical inactivity, and sleep disturbance. These findings may help strategically tailor multidomain dementia intervention programs to have the greatest impact in the Canadian population.

Background Alzheimer’s disease (AD) is a form of dementia that impairs memory, language, and daily functioning. With disease progression, AD patients reportedly experience disturbances in their awareness of self, others, and their environment. These disturbances are associated with unfavourable clinical outcomes, which prompts critical questions about how AD patients experience the world around them. The present study utilizes a validated neuroimaging paradigm to ‘map’ conscious experiences through changes in brain activity. The premise is that similarity (i.e., synchrony) in conscious experiences of different people can be detected by investigating activity in fronto‐parietal areas linked with higher‐order processing essential for plot‐following. This paradigm was previously used to assess conscious states of behaviorally non‐responsive brain‐injured patients, showing that the internal mental experience of some patients was similar to that of healthy controls. Methods In this study, patients with mild‐moderate AD (n = 9) and age‐matched healthy controls (n = 29) underwent a 40‐minute functional near‐infrared spectroscopy (fNIRS) scan. During the scan, participants watched two short movies, each with an intact‐ and scrambled‐plot version. Scrambled versions were included to demonstrate that synchrony was associated with higher‐order processing rather than the mere presentation of audio‐visual stimuli. Inter‐subject correlations (i.e., Pearson correlation coefficients between the hemodynamic activity of one or more AD patients and the remaining participants, including healthy controls) were used as the metric for synchrony. Results Compared to the scrambled plot conditions, healthy controls showed robust synchronization in the frontal and parietal regions in the intact‐plot conditions. AD patients, in contrast, did not demonstrate a consistent pattern of synchronization in these regions during the intact‐plot conditions. Single‐subject analyses (i.e., comparing individual patients to the control group) further revealed that only one AD patient exhibited some degree of synchronization with the healthy controls during the audio‐visual stimuli. Conclusion These preliminary findings indicate that AD patients may be experiencing the world differently from healthy individuals. The variability noted in synchronization across AD patients may be reflective of the heterogeneity in disease‐related impairments. Understanding deficits and patient needs from the lens of impaired conscious processing could support disease prognosis and promote improvements in person‐centered care.

Background Neuropsychiatric symptoms (NPS) constitute a major challenge for patients with Alzheimer’s disease (AD). We have recently demonstrated that in AD, overall NPS burden is significantly associated with patient function. However, few studies have examined the relationship between specific symptom clusters with neurological biomarkers. Therefore, we identified NPS clusters in AD and explored their association with structural neuroimaging markers. Method Participants with AD (N = 111) were included from the Ontario Neurodegenerative Disease Research Initiative (ONDRI). NPS were assessed using the neuropsychiatric inventory questionnaire (NPI‐Q), and symptom clusters were identified through exploratory factor analysis. The Semi‐Automatic Brain Region Extraction (SABRE) pipeline was used to compute regional cortical thickness and subcortical volumes using participant MRI data. We then evaluated correlations between symptom clusters with subcortical volumes and regional cortical thickness. Result Factor analysis identified four symptom clusters explaining 62% of the variance. These were labeled as “behavioral” (disinhibition, irritability, motor disturbance, and agitation), “psychotic” (hallucinations, delusions, and euphoria), “neurovegetative” (apathy and appetite), and “affective” (depression, anxiety, nighttime behavior) clusters. The psychotic cluster was associated with increased cortical thickness in bilateral frontal regions, the left inferior parietal lobe (r=0.23, p=0.02), and with left anterior cingulate volumes (r=0.21, p=0.03). The neurovegetative cluster was associated with reductions in volume among bilateral frontal and right‐sided temporal and parietal regions. The affective cluster was associated with increased left anterior cingulate volume (r=0.21, p=0.03). Conclusion NPS symptom clusters in AD separate into behavioral, psychotic, neurovegetative, and affective dimensions. These symptom groups demonstrate unique associations with neuroimaging markers.

Background Social cognition is impacted early in the disease progression of many neurodegenerative diseases (ND). The Salience network (SN) is an intrinsically connected brain network responsible for social cognitive function. Keys hubs of this brain network, the anterior insula (AI) and anterior cingulate cortex (ACC), are reported to incorporate ‘bottom‐up’ signals from subcortical regions such as the amygdala and periaqueductal gray (PAG), but this mechanism and the subcortical contribution to SN connectivity is poorly understood. Our aim was to investigate the contribution of cortical and subcortical structures to SN functional connectivity and to social cognition across NDs. Method 76 participants (21 Alzheimer’s disease, 13 behavioural variant frontotemporal dementia, and 42 Parkinson’s disease) from the Ontario Neurodegenerative Research Initiative (ONDRI) baseline or one‐year follow up visits with resting state fMRI, Montreal Cognitive Assessment (MoCA) total scores, and informant‐reported socioemotional sensitivity scores using the Revised Self‐Monitoring Scale (RSMS) were included (higher score, indicating higher function). All groups were age‐ and sex‐matched. Fisher‐transformed correlation coefficients of functional connectivity from an ROI‐to‐ROI analysis between cortical and subcortical SN ROIs were used to create a mean cortical SN value and mean subcortical SN value to use in linear regression modelling with behavioural scores. Result Mean cortical and subcortical SN connectivity were significantly associated with RSMS total score (b = 2.94, p = 0.041; (b = 3.60, p = 0.014, respectively), independent of cognitive function, with higher connectivity predicting higher score. The interaction between cortical and subcortical connectivity was not significantly associated with RSMS total score. Mean cortical and subcortical connectivity was significantly associated with RSMS‐EX (expressive behaviour of others) and RSMS‐SP (self‐presentation) subscores (b = 1.36, p = 0.049; b = 1.44, p = 0.040; b coef = 1.58, p‐value = 0.033; b coef = 2.15, p‐value = 0.005, respectively). Conclusion Our results indicate a stronger contribution of subcortical structures to social cognition‐related functional connectivity across various neurodegenerative diseases. Despite previous associations with cortical regions, our evidence suggests that alterations in subcortical structures mediate changes in social cognition. Further exploration in larger cohorts is necessary, as impaired social cognition in patients with ND is associated with increased caregiver distress.

Background Apathy in patients with Alzheimer’s disease (AD) is associated with significant morbidity. We examined whether interactions between genetic variants related to neurotransmitter systems and regional brain atrophy are associated with apathy in patients with mild cognitive impairment (MCI) and AD. Method For 1162 participants in the Alzheimer’s Disease Neuroimaging Initiative, including those with AD, MCI and cognitively normal individuals, a partial least squares correspondence analysis (PLS‐CA) modeled interactions between single nucleotide polymorphisms (SNPs), structural whole‐brain imaging variables, and apathy. Result An interaction between apathy, the possession of an APOE (apolipoprotein E) ε4 allele combined with minor homozygosity for the DAT1 (dopamine transporter 1) gene, and brain atrophy. Conclusion The results point to an association of a dopaminergic genetic marker and apathy in AD and may inform future design of clinical trials of apathy, as well as new treatment targets.

Background Older adults with type 2 diabetes (T2D) are more likely to develop Alzheimer’s disease (AD) due to impaired brain metabolism. Although the underlying mechanisms of this relationship are largely unknown, lower levels of brain‐derived neurotrophic factor (BDNF) –which promotes hippocampal neurogenesis in adulthood– and atrophy of the hippocampus are evident in patients with T2D and dementia, possibly linking the two conditions. The hippocampus is comprised of multiple subfields, each with their respective functions, cellular composition, and age‐related sensitivity. In particular, the dentate gyrus, known for its key role in memory processing, is one of the only regions in the brain capable of producing new neurons through BDNF. At the onset of dementia, the rapid loss of hippocampal tissue results in functional disconnection with other areas of the brain involved in cognition, making hippocampal atrophy a biomarker for cognitive decline. Understanding region‐specific hippocampal atrophy during the early stages of diabetes may provide insight into the link between T2D and brain atrophy that is characteristic of AD. Therefore, our study investigates the relationship between BDNF levels and hippocampal subfield volumes in older adults at risk for T2D. Method Sixty older adults (aged 60‐80 years, mean = 68.64, 72.34% female) at risk for diabetes completed demographic and medical history questionnaires. Diabetes risk was assessed using HbA1c, BMI, and a diabetes questionnaire. BDNF serum levels were analyzed from blood samples using an enzyme‐linked immunoassay test (ELISA). Anatomical T1 and T2 weighted brain images were collected via 3T MRI and analyzed using HippUnfold – a novel segmentation tool that accounts for individual variability in the folding patterns of hippocampal subregions. Result Preliminary results show that higher diabetes risk was associated with lower BDNF levels and reduced hippocampal subfield volumes. In addition, BDNF serum levels were predictive of hippocampal subfield volumes, specifically in the dentate gyrus. Conclusion Findings demonstrate a relationship between diabetes risk factors, BDNF, and hippocampal subfield volumes (i.e., dentate gyrus) in regions where neurogenesis continues throughout adulthood. As life expectancy and diabetes incidence increases, our study urges the development and application of interventions aimed at preventing the progression of diabetes‐related neurodegeneration.

BACKGROUND Stroke secondary to intracranial atherosclerotic disease (ICAD) is associated with high recurrence risk despite currently available secondary prevention strategies. In patients with systemic atherosclerosis, a significant reduction of stroke risk with no increase in intracranial or fatal hemorrhage was seen when rivaroxaban 2.5 mg twice daily was added to aspirin. However, there are no trials in ICAD using this combination. To facilitate the design of future ICAD trials, the CATIS-ICAD study (Combination Antithrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease) assessed (1) the feasibility of recruitment, (2) the safety of low-dose rivaroxaban plus aspirin compared with standard-of-care antiplatelet therapy, and (3) trends toward efficacy. METHODS This was a prospective, randomized, open-label, blinded end point pilot trial conducted in 10 Canadian centers. Eligible participants aged ≥40 years, with acute ischemic stroke or high-risk transient ischemic attack, were randomly assigned in a 1:1 ratio to receive low-dose rivaroxaban plus aspirin or aspirin alone within 7 to 100 days of their index event. The primary safety outcome was hemorrhagic stroke. The main efficacy end point was the composite of ischemic stroke or covert brain infarct on magnetic resonance imaging at the end of the study. RESULTS A total of 101 participants were randomized. Average enrollment was 10 participants/site per year. Average follow-up was 20 months. Median time from index stroke to randomization was 67 days. The median age of participants was 67 years (±10.94), and 29% of participants were women. There was no hemorrhagic stroke in either arm. The composite efficacy outcome was less frequent in the combination arm (15.7%) compared with the aspirin arm (24.0%), with a hazard ratio of 0.78 ([95% CI, 0.32–1.93]; P =0.59) favoring the intervention. CONCLUSIONS A multicenter randomized trial comparing the combination of low-dose rivaroxaban and aspirin in patients with recent ischemic stroke or transient ischemic attack due to ICAD is feasible and appears safe without an increased risk of hemorrhagic stroke. A numerical trend toward efficacy for the composite primary end point of symptomatic ischemic stroke and covert infarcts was observed. These findings will inform the design of a phase III trial. REGISTRATION URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04142125.