BACKGROUND:In Parkinson's disease (PD) and dementia with Lewy bodies (DLB), the cholinergic system has been implicated in cognitive and gait decline. The nucleus basalis of Meynert (NBM), within the substantia innominata (SI), is the main cholinergic nucleus projecting to the cortex. In this study, the relationship between atrophy of the SI on cognitive phenotypes and quantitative gait performance was evaluated in relation to gray matter (GM) volume. METHODS:Ninety-nine participants - 20 control, 42 PD with normal cognition (PD-NC), 19 PD with mild cognitive impairment (PD-MCI) and 18 PD dementia or DLB patients (PDD/DLB) - were examined. Measures included Montreal Cognitive Assessment (MoCA) score, motor symptom severity, quantitative gait analysis measures and dual-task cost (DTC) to gait speed. Manual measurement of SI volume was performed on T1 MRI scans; automated methods were used for GM volumes. The relationships between gait changes, volumetric imaging and clinical measures were assessed. RESULTS:Smaller SI volumes were seen in PD-MCI and PDD/DLB subjects adjusting for age. SI and GM atrophy were both associated with greater step length variability, and GM was associated with increased DTC to gait speed. These were not significant after adjusting for the false discovery rate. Lower MoCA score was associated with impairments in gait speed, DTC to gait speed and gait variability. CONCLUSION:The SI was associated with cognitive impairment in participants with Lewy body diseases. However, more widespread cortical atrophy may be better related to selected cognitive aspects of gait (DTC to gait speed with animal fluency).

Introduction Across the dementia-free cognitive spectrum, later-life emergent and persistent changes in behavior and personality, known as mild behavioral impairment (MBI), can be an early manifestation of Alzheimer’s disease (AD). Few studies have directly quantified the difference in odds of AD pathology between older adults with and without MBI. We examined the relationship between MBI and AD biomarker profiles in older adults without dementia. Methods We used baseline data from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study. Participants (n=242, 71.5±6.6 years old, 56.2% female) were cognitively unimpaired (33.1%) or had subjective cognitive decline (12.4%) or mild cognitive impairment (54.5%). Biomarker profiles were generated based on Gaussian mixture modeling of standardized, age- and sex-adjusted multi-modal biomarker values and AD polygenic risk scores (PRS). The biofluid biomarkers included plasma amyloid-β 42/40 (Aβ42/40), phosphorylated tau-181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) measured using Single Molecule Array assays. Imaging biomarkers included mean cortical thickness in an AD meta-region-of-interest (entorhinal, inferior temporal, middle temporal cortices, fusiform gyrus) and bilateral hippocampal volume derived from T1-weighted structural magnetic resonance imaging using FreeSurfer v7.The GMM identified three biomarker profiles, categorized post-hoc as: normal (normal plasma/imaging biomarkers, low PRS), non-AD neurodegeneration (abnormal GFAP/NfL/thickness, normal Aβ42/40, p-tau181, hippocampal volume), and AD-consistent (all biomarkers abnormal, high PRS). For the subsequent analysis, participants classified with non-AD neurodegeneration profiles (n=9) were excluded, leaving 180 (74.4%) normal and 62 (25.6%) AD-consistent participants. MBI was assessed using the informant-rated MBI Checklist, with scores ≥7 used to classify MBI+ status.Logistic regression examined the association between MBI status (exposure) and biomarker profile (normal vs AD-consistent; outcome). Models adjusted for age, sex, education, and Montreal Cognitive Assessment (MoCA) total score to determine incremental validity. MBI domain analyses were also conducted with status defined as a presence (domain score≥1) or absence (domain score=0) of symptoms. Results The odds of having an AD-consistent biomarker profile were 2.26 (95% CI: [1.15-4.43], p=.02) times greater for participants with MBI than those without, even after accounting for MoCA total score. Odds differed significantly for the MBI decreased motivation domain (odds ratio [OR]=2.04, 95% CI: [1.06-3.93], p=.03). Similar associations were observed for affective dysregulation (OR=1.73, 95% CI: [0.93-3.24], p=.08) and impulse dyscontrol (OR=1.81, 95% CI: [0.97-3.40], p=.06), although with slightly weaker effect sizes and not statistically significant. Conclusions Older adults with MBI are more likely to exhibit biomarker profiles consistent with AD that cannot be fully explained by global performance on a common cognitive screening tool, such as the MoCA. These findings support MBI as a clinically meaningful marker of preclinical and prodromal AD that can be integrated into standard clinical assessment for improved diagnostic precision.

People living with dementia (PLWD) were disproportionately impacted by the COVID-19 pandemic, experiencing high mortality rates in the initial waves. However, factors contributing to their increased risk of death following COVID-19 infection remain unclear. Given that PLWD are a heterogenous population with varying susceptibility to negative health outcomes, this study aimed to identify independent factors associated with 30-day COVID-19 mortality among PLWD and vulnerable subgroups of PLWD. We conducted a retrospective cohort analysis using administrative data from March 1st 2020 to December 1st 2020, in Alberta, Canada. We examined the association between an outcome variable created to examine mortality in the 30-days following COVID-19 infection and factors related to the demographics and health (e.g., age, comorbidities), health service use (e.g., past physician utilization), and environment (e.g., community or long-term care) of PLWD in our study cohort and subgroups of our study cohort based on age, sex, and living setting (community, long-term care). Among our study cohort of PLWD (N = 1526), 28

Background: The Montreal Cognitive Assessment (MoCA) and Rowland Universal Dementia Assessment Scale (RUDAS) are tests used to detect mild cognitive impairment (MCI) and dementia. However, it has been suggested that the MoCA may not be appropriate for diverse populations, and that the relatively newer RUDAS may be better suited as a universal cognitive test. Methods: The MoCA and RUDAS were administered at baseline visits for participants enrolled in the Prospective Registry of Persons with Memory Symptoms (PROMPT). Test scores were compared for patients with different levels of educational attainment, first language, and race using the Kruskal-Wallis test. Results: The difference in MoCA (0.029) and RUDAS (0.0041) scores between patients with different levels of educational attainment (n = 141) was significant. The difference in MoCA (0.62) and RUDAS (0.78) scores between patients with a different first language (n = 141) was not significant. The difference in MoCA (0.64) and RUDAS (0.96) scores between patients of different race (n = 141) was not significant. Conclusions: The difference between MoCA and RUDAS scores remained consistent regardless of level of educational attainment, first language and race. The results suggest that the RUDAS may not be more appropriate than the MoCA in detecting MCI and dementia across diverse populations.

Background: There are many cognitive tests that detect mild cognitive impairment (MCI) and dementia such as the Montreal Cognitive Assessment (MoCA) and Rowland Universal Dementia Assessment Scale (RUDAS). The comparative performance of these screening tests for identifying MCI and dementia is unknown. Methods: The MoCA and RUDAS were administered during baseline visits for patients in the Calgary Neurosciences Program. Those that enrolled in the Prospective Registry of Persons with Memory Symptoms (PROMPT) had their scores related to their final clinical diagnosis. Cut-off scores of 26 for the MoCA and 22 for the RUDAS were used to indicate a positive result. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of both cognitive scores were compared. Results: The sensitivity, specificity, PPV, NPV, and accuracy of the MoCA (n = 125) was 89.3%, 72.7%, 93.9%, 59.3%, and 86.4%, respectively. The sensitivity, specificity, PPV, NPV, and accuracy of the RUDAS (n = 125) was 47.6%, 100%, 100%, 29.0%, 56.8%, respectively. Conclusions: In patients with cognitive complaints presenting to a specialist clinic, the MoCA was more sensitive and accurate than the RUDAS for a final clinician diagnosis of mild cognitive impairment or dementia when using the standard cut-offs.