Changes in brain chondroitin (CS)-O, CS-E, and CS-sulfate-glycosaminoglycan (CS-GAG) hypersulfation correspond to altered cognitive function. Demented (Alzheimer’s disease) and non-demented individuals were stratified by pathology according to Braak stage: B0/1, Braak 0-II (blue); B2, Braak III/IV (yellow); and B3, Braak V/VI (red). A, Mini-Mental State Examination (MMSE) scores negatively associate with phosphorylated tau (p-tau) inclusion number in the middle frontal gyrus (MFG). B, MMSE scores positively associate with CS-O and negatively associate with CS-E and (C) negatively associate with CS-GAG hypersulfation in the MFG. D, Model depicting changes in perineuronal net CS-GAG sulfation code in relation to AD clinicopathology. A-C, n = 29 subjects; mean ± standard deviation. Data were analyzed using linear regression with the 95% confidence bands shown in gray