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Comparative Study
, 65 (6), 776-85

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

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Comparative Study

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

Joseph J Locascio et al. Arch Neurol.

Abstract

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.

Figures

Figure 1
Figure 1
Raw scores on the Blessed Dementia Scale (BDS) (A) and the Weintraub Activities of Daily Living Scale (ADL) (B) across the duration of Alzheimer disease in years. Thin lines connect scores for the same person. Thick lines indicate ordinary least squares linear regression line (solid red lines) and quadratic curve (dashed blue lines). Unlike the random coefficient analyses, the ordinary least squares lines are blind to the within-subject vs between-subject distinction and the correlation of scores across time within a subject. The ordinary least squares lines tend to underestimate the within-subject rates, which is noticeable in the figure.
Figure 2
Figure 2
Illustrative mean scores on the Blessed Dementia Scale (BDS) across time predicted by the fitted model in the longitudinal analysis for selected levels of amyloid β-protein 40 (A), amyloid β-protein 42 (B), and log-transformed, high-sensitivity C-reactive protein (C) and an example time span (maximum likelihood estimates). For this graph, age was set at 75 years and years as a patient in the memory clinic at zero when duration of Alzheimer disease was 3 years, in correspondence to the approximate relation of their respective actual mean values at first visit in the data. Age, years as a clinic patient, and duration of illness were then increased in tandem. Illustrative levels of the biomarker were chosen to correspond to the 1st, 25th, 50th (median), 75th, and 99th percentiles of its distribution. Thus, the spacing between the lines reflects the shape of the distribution. The vertical dotted line indicates the point at which the patient was first seen in the memory clinic, that is, where years as a patient in the memory clinic was zero in the model.
Figure 3
Figure 3
Illustrative mean scores on the Weintraub Activities of Daily Living Scale (ADL) across time predicted by the fitted model in the longitudinal analysis for selected levels of amyloid β-protein 42 (A) and the log-transformed, high-sensitivity C-reactive protein (B) and time span (maximum likelihood estimates). Age at first visit was set at 75 years and years as a patient in the memory clinic at zero. Years of educational achievement was also significantly related to better scores and was set at the grand mean (14 years) for these predicted values. Illustrative levels of the biomarker were chosen to correspond to the 1st, 25th, 50th (median), 75th, and 99th percentiles of its distribution. The vertical line indicates the point at which the patient was first seen in the memory clinic, that is, where years as a patient in the memory clinic was zero in the model.

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