• Kristine Yaffe, Andrea Weston, Neill R Graff-Radford, Suzanne Satterfield, Eleanor M Simonsick, Steven G Younkin, Linda H Younkin, Lewis Kuller, Hilsa N Ayonayon, Jingzhong Ding, and Tamara B Harris.
• Department of Psychiatry, University of California, San Francisco, and San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121, USA. kristine.yaffe@ucsf.edu
• JAMA. 2011 Jan 19; 305 (3): 261266261-6.

ContextLower plasma β-amyloid 42 and 42/40 levels have been associated with incident dementia, but results are conflicting and few have investigated cognitive decline among elders without dementia.ObjectiveTo determine if plasma β-amyloid is associated with cognitive decline and if this association is modified by measures of cognitive reserve.Design, Setting, And ParticipantsWe studied 997 black and white community-dwelling older adults from Memphis, Tennessee, and Pittsburgh, Pennsylvania, who were enrolled in the Health ABC Study, a prospective observational study begun in 1997-1998 with 10-year follow-up in 2006-2007. Participant mean age was 74.0 (SD, 3.0) years; 55.2% (n = 550) were female; and 54.0% (n = 538) were black.Main Outcome MeasuresAssociation of near-baseline plasma β-amyloid levels (42 and 42/40 measured in 2010) and repeatedly measured Modified Mini-Mental State Examination (3MS) results.ResultsLow β-amyloid 42/40 level was associated with greater 9-year 3MS cognitive decline (lowest β-amyloid tertile: mean change in 3MS score, -6.59 [95% confidence interval [CI], -5.21 to -7.67] points; middle tertile: -6.16 [95% CI, -4.92 to -7.32] points; and highest tertile: -3.60 [95% CI, -2.27 to -4.73] points; P < .001). Results were similar after multivariate adjustment for age, race, education, diabetes, smoking, and apolipoprotein E [APOE ] e4 status and after excluding the 72 participants with incident dementia. Measures of cognitive reserve modified this association whereby among those with high reserve (at least a high school diploma, higher than sixth-grade literacy, or no APOE e4 allele), β-amyloid 42/40 was less associated with multivariate adjusted 9-year decline. For example, among participants with less than a high school diploma, the 3MS score decline was -8.94 (95% CI, -6.94 to -10.94) for the lowest tertile compared with -4.45 (95% CI, -2.31 to -6.59) for the highest tertile, but for those with at least a high school diploma, 3MS score decline was -4.60 (95% CI,-3.07 to -6.13) for the lowest tertile and -2.88 (95% CI,-1.41 to -4.35) for the highest tertile (P = .004 for interaction). Interactions were also observed for literacy (P = .005) and for APOE e4 allele (P = .02).ConclusionLower plasma β-amyloid 42/40 is associated with greater cognitive decline among elderly persons without dementia over 9 years, and this association is stronger among those with low measures of cognitive reserve.

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