Association of Plasma β-Amyloid Level and Cognitive Reserve With Subsequent Cognitive Decline | Dementia and Cognitive Impairment | JAMA | JAMA Network
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Original Contribution
January 19, 2011

Association of Plasma β-Amyloid Level and Cognitive Reserve With Subsequent Cognitive Decline

Author Affiliations

Author Affiliations: Departments of Psychiatry (Dr Yaffe and Ms Weston), Neurology (Dr Yaffe), and Epidemiology and Biostatistics (Drs Yaffe and Ayonayon), University of California, San Francisco, and San Francisco Veterans Affairs Medical Center (Dr Yaffe), San Francisco; Departments of Neurology (Dr Graff-Radford) and Neuroscience (Drs S. G. Younkin and L. H. Younkin), Mayo Clinic, Jacksonville, Florida; Department of Preventive Medicine, University of Tennessee at Memphis (Dr Satterfield); Clinical Research Branch (Dr Simonsick) and Laboratory of Epidemiology, Demography, and Biometry (Dr Harris), National Institute on Aging, Baltimore, Maryland; Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Kuller); and Department of Gerontology and Geriatric Medicine, Wake Forest University Medical Center, Winston-Salem, North Carolina (Dr Ding).

JAMA. 2011;305(3):261-266. doi:10.1001/jama.2010.1995

Context Lower 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.

Objective To determine if plasma β-amyloid is associated with cognitive decline and if this association is modified by measures of cognitive reserve.

Design, Setting, and Participants We 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 Measures Association of near-baseline plasma β-amyloid levels (42 and 42/40 measured in 2010) and repeatedly measured Modified Mini-Mental State Examination (3MS) results.

Results Low 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).

Conclusion Lower 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.