Increased levels of Osteopontin are associated with dementia in the presence of cerebral small vessel disease

Abstract Background Osteopontin is a proinflammatory cytokine associated with systemic vascular, inflammatory, and autoimmune diseases. It has been recently implicated in neuroinflammation and neurodegeneration. We hypothesized that plasma osteopontin is a deleterious neuroinflammatory marker increased in people with dementia and cerebral small vessel disease (CSVD). Method We conducted a pilot study in participants in the longitudinal multi‐ethnic Northern Manhattan Study (NOMAS). Three groups were selected based on their dementia status and evidence of subclinical CSVD, and chosen to be similar in age, sex, and education attainment: No Dementia/No CSVD (n = 19), Dementia/No CSVD (n = 22), and Dementia+CSVD (n = 21). Dementia (any type) was diagnosed by consensus adjudication following a series of comprehensive neuropsychological assessments and a review of medical history. CSVD was indicated by silent brain infarcts, perivascular spaces, cerebral microbleeds, and white matter hyperintensity volumes on MRI. Osteopontin was measured by quantitative solid‐phase ELISA. Multinomial logistic regression was used to examine the difference in osteopontin levels across groups, adjusting for key determinants of CSVD and neurodegeneration in NOMAS, including age, race/ethnicity, BMI, and brain volume. Result Osteopontin levels were substantially elevated in the Dementia+ CSVD group (mean = 70.69±39.00 ng/ml) and only slightly increased in the Dementia/No CSVD group (mean = 45.46±19.11) compared to the No dementia/No CSVD group (mean = 36.43±15.72). Osteopontin was associated with dementia+CSVD (Odds Ratio (OR) per ng/ml = 1.06, 95%CI 1.02‐1.11) in unadjusted analysis, and this remained consistent and significant after adjusting for covariates, including brain volume. Osteopontin was strongly correlated with WMHV (Pearson r = 0.46, p = 0.0001), but not with other components of CSVD. Conclusion In this pilot study, we observed a significant relationship between increased levels of osteopontin and dementia. This link is predominately driven by vascular contributions to dementia through the presence of CSVD, specifically through the burden of white matter lesions on MRI. Brain volume, a marker of neurodegeneration, does not seem to influence this relationship. Our study provides further evidence to suggest that underlying white matter disease and CSVD are likely targets of deleterious osteopontin expression in dementia

Osteopontin is associated with dementia in the presence of cerebral small vessel disease

Background: Osteopontin (OPN) is a proinflammatory cytokine that has been recently implicated in neuroinflammation and neurodegeneration. We hypothesized that an increase in plasma osteopontin is a deleterious neuroinflammatory marker in people with dementia and cerebral small vessel disease (CSVD).Methods: A pilot study was conducted on participants in the Northern Manhattan Study (NOMAS). Three groups were selected based on their dementia status and evidence of subclinical CSVD and chosen to be similar in age, sex, and education attainment: No dementia/No CSVD (n=19), Dementia/No CSVD (n=22), and Dementia+CSVD (n=21). Dementia (any type) was diagnosed by consensus adjudication following a series of comprehensive neuropsychological assessments and a review of the medical history. CSVD was indicated by silent brain infarcts, enlarged perivascular spaces, cerebral microbleeds, and white matter hyperintensity volumes (WMHV) on MRI. Multinomial logistic regression was used to examine the difference in OPN levels across groups, adjusting for key determinants of CSVD and neurodegeneration. Results: Plasma osteopontin levels were elevated in the Dementia+CSVD group (mean=70.69 & PLUSMN;39.00 ng/ml) but not in the Dementia/No CSVD group (mean=45.46 & PLUSMN;19.11 ng/ml) compared to the No dementia/No CSVD group (mean=36.43 & PLUSMN;15.72 ng/ml). Osteopontin was associated with Dementia+CSVD (Odds Ratio (OR) per ng/ml=1.06, 95%CI 1.02-1.11) after adjusting for covariates, including brain volume. OPN was strongly correlated with WMHV (Spearman's rank correlation =0.46, p=0.0001), but not with other components of CSVD. Conclusion: In this pilot, greater levels of plasma osteopontin were associated with dementia with evidence of CSVD. This link was predominately driven by the contribution of OPN to dementia through the burden of white matter lesions