Relationships of Cognitive Measures with Cerebrospinal Fluid but Not Imaging Biomarkers of Alzheimer Disease Vary between Black and White Individuals.

OBJECTIVE: Biomarkers of Alzheimer disease vary between groups of self-identified Black and White individuals in some studies. This study examined whether the relationships between biomarkers or between biomarkers and cognitive measures varied by racialized groups. METHODS: Cerebrospinal fluid (CSF), amyloid positron emission tomography (PET), and magnetic resonance imaging measures were harmonized across four studies of memory and aging. Spearman correlations between biomarkers and between biomarkers and cognitive measures were calculated within each racialized group, then compared between groups by standard normal tests after Fisher's Z-transformations. RESULTS: The harmonized dataset included at least one biomarker measurement from 495 Black and 2,600 White participants. The mean age was similar between racialized groups. However, Black participants were less likely to have cognitive impairment (28% vs 36%) and had less abnormality of some CSF biomarkers including CSF Aß42/40, total tau, p-tau181, and neurofilament light. CSF Aß42/40 was negatively correlated with total tau and p-tau181 in both groups, but at a smaller magnitude in Black individuals. CSF Aß42/40, total tau, and p-tau181 had weaker correlations with cognitive measures, especially episodic memory, in Black than White participants. Correlations of amyloid measures between CSF (Aß42/40, Aß42) and PET imaging were also weaker in Black than White participants. Importantly, no differences based on race were found in correlations between different imaging biomarkers, or in correlations between imaging biomarkers and cognitive measures. INTERPRETATION: Relationships between CSF biomarkers but not imaging biomarkers varied by racialized groups. Imaging biomarkers performed more consistently across racialized groups in associations with cognitive measures. ANN NEUROL 2024;95:495-506.

MS and Disability Progression in Latin America, Africa, Asia and the Middle East: A Systematic Review.

BACKGROUND: There is evidence of an increased prevalence and disease burden of Multiple Sclerosis (MS) in parts of the world where the risk was once considered low, such as Latin America (LA), Sub-Saharan Africa, Asia and the Middle East-North Africa (MENA). Despite the growing number of clinical reports, the phenotype and course of MS in these regions remains understudied compared with Europe and North America. We aimed to investigate MS phenotypes and long-term clinical outcomes across these regions. METHOD: A Boolean search of the medical literature was conducted between January 1980 and April 30, 2020. PubMed, SCOPUS, Global Health, and the Cochrane databases, were used to identify all relevant citations. Articles were collated and managed on Covidence® software. We independently appraised the articles for meeting study criteria and for quality using the Critical Appraisal Skills Program (CASP) and the Specialist Unit for Review Evidence (SURE) system. RESULTS: A total of 1,639 studies were imported for screening. After removing 545 duplicates, two authors assessed 1,094 abstracts and selected 515 for full-text screening. 72 articles met study criteria, including 19 studies from LA, 4 from sub-Saharan Africa, 24 from Asia and 25 from MENA. The overall sex ratio was 2.5:1 (female: male). Disability was assessed using the Expanded Disability Status Scale (EDSS). Longitudinal disability progression and time to standard endpoints was compared by region and with relevant Western reports. Patients with MS living in the MENA region appear to reach disability milestones faster than those in the Western world, although this finding is not uniform. South Asia shows distinct disability features compared with East Asia, more closely resembling those of the West. Disease morbidity in East Asia appears more benign than in the West after careful exclusion of neuromyelitis optica spectrum disorder cases. Populations in LA tend to have similar MS features to the Western world, but some exceptions exist, including African descendants that reach disability milestones earlier. Using all studies with appropriate survival analysis, the mean time to EDSS 6.0 was 16.97 years with a heterogeneity index of 24.59. CONCLUSION: The clinical phenotypes and disability progression of MS in LA, Africa, Asia and the MENA region have similarities to Western MS. In some regions and subpopulations there is evidence of a more aggressive course, possibly due to a combination of genetic and environmental factors. More population-based longitudinal data are needed, particularly in Sub-Saharan Africa.

The CSF Profile Linked to Cortical Damage Predicts Multiple Sclerosis Activity.

OBJECTIVE: Intrathecal inflammation correlates with the grey matter damage since the early stages of multiple sclerosis (MS), but whether the cerebrospinal fluid (CSF) profile can help to identify patients at risk of disease activity is still unclear. METHODS: We evaluated the association between CSF levels of 18 cytokines, previously found to be associated to grey matter damage, and the disease activity, among 99 patients with relapsing-remitting MS, who underwent blinded clinical and 3 T magnetic resonance imaging (MRI) evaluations for 4 years. Groups with evidence of disease activity (EDA) or no evidence of disease activity (NEDA; occurrence of relapses, new white matter lesions, and Expanded Disability Status Scale [EDSS] change) were identified. Cortical lesions and the annualized cortical thinning were also evaluated. RESULTS: Forty-one patients experienced EDA and, compared to the NEDA group, had at diagnosis higher CSF levels of CXCL13, CXCL12, IFNγ, TNF, sCD163, LIGHT, and APRIL (p < 0.001). In the multivariate analysis, CXCL13 (hazard ratio [HR] = 1.35; p = 0.0002), LIGHT (HR = 1.22; p = 0.005) and APRIL (HR = 1.78; p = 0.0001) were the CSF molecules more strongly associated with the risk of EDA. The model, including CSF variables, predicted more accurately the occurrence of disease activity than the model with only clinical/MRI parameters (C-index at 4 years = 71% vs 44%). Finally, higher CSF levels of CXCL13 (ß = 4.7*10-4 ; p < 0.001), TNF (ß = 3.1*10-3 ; p = 0.004), LIGHT (ß = 2.6*10-4 ; p = 0.003), sCD163 (ß = 4.3*10-3 ; p = 0.009), and TWEAK (ß = 3.4*10-3 ; p = 0.024) were associated with more severe cortical thinning. INTERPRETATION: A specific CSF profile, mainly characterized by elevated levels of B-cell related cytokines, distinguishes patients at high risk of disease activity and severe cortical damage. The CSF analysis may allow stratifications of patients at diagnosis for optimizing therapeutic approaches. ANN NEUROL 2020;88:562-573.