Plasma Amyloid β-Protein and C-reactive Protein in Relation to the Rate of Progression of Alzheimer Disease

OBJECTIVE: To examine whether plasma markers of amyloid precursor protein metabolism (amyloid beta-protein ending in Val-40 [Abeta40] and Ala-42 [Abeta42]), inflammation (high-sensitivity C-reactive protein), and folic acid metabolism (folic acid, vitamin B(12), and total homocysteine levels) are associated with the rate of cognitive and functional decline in persons with Alzheimer disease. DESIGN: Longitudinal study across a mean (SD) of 4.2 (2.6) years with assessments at approximately 6- to 12-month intervals. SETTING: Outpatient care. PATIENTS: A cohort of 122 patients having a clinical diagnosis of probable Alzheimer disease, each with at least 2 assessments across time. MAIN OUTCOME MEASURES: Scores on the cognitive Information-Memory-Concentration subscale of the Blessed Dementia Scale and the functional Weintraub Activities of Daily Living Scale. RESULTS: Low plasma levels of Abeta40, Abeta42, and high-sensitivity C-reactive protein were associated with a significantly more rapid cognitive decline, as indexed using the Blessed Dementia Scale, than were high levels. Low levels of Abeta42 and high-sensitivity C-reactive protein were significantly associated with more rapid functional decline on the Weintraub Activities of Daily Living Scale than were high levels. These plasma markers contributed about 5% to 12% of the variance accounted for on the Blessed Dementia Scale and the Activities of Daily Living Scale by fixed-effects predictors. Measures of folic acid metabolism were not associated with changes on either the Blessed Dementia Scale or the Activities of Daily Living Scale. CONCLUSIONS: Plasma markers of amyloid precursor protein metabolism and C-reactive protein may be associated with the rate of cognitive and functional decline in patients with Alzheimer disease.