Association of plasma beta-amyloid level and cognitive reserve with subsequent cognitive decline.
BACKGROUND
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.


METHODS
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.


METHODS
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).


CONCLUSIONS
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.
Department of Psychiatry, University of California, San Francisco, and San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121, USA. kristine.yaffe@ucsf.edu
Kristine
K
Yaffe
Andrea
A
Weston
Neill R
NR
Graff-Radford
Suzanne
S
Satterfield
Eleanor M
EM
Simonsick
Steven G
SG
Younkin
Linda H
LH
Younkin
Lewis
L
Kuller
Hilsa N
HN
Ayonayon
Jingzhong
J
Ding
Tamara B
TB
Harris
D000368:Aged; D016229:Amyloid beta-Peptides / Q000097:blood*; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D044383:Black People / Q000235:genetics; D003072:Cognition Disorders / Q000097:blood*; D058245:Cognitive Reserve; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D010414:Pennsylvania; D010446:Peptide Fragments / Q000097:blood; D013714:Tennessee; D001741:Black or African American
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D010446:Peptide Fragments; C538897:amyloid beta-protein (40-42)
Alzheimer Dis Assoc Disord. 2002 Jul-Sep;16(3):187-90
12218650
Neurobiol Aging. 2010 Mar;31(3):357-67
18486992
Curr Neurol Neurosci Rep. 2004 Sep;4(5):374-80
15324603
Arch Neurol. 2003 Jul;60(7):958-64
12873852
Diabetes Educ. 2004 Mar-Apr;30(2):263-73
15095516
Neurology. 2008 May 6;70(19):1664-71
18401021
Neurology. 2006 Jun 27;66(12):1837-44
16801647
Neurology. 2007 May 15;68(20):1718-25
17502554
J Clin Psychiatry. 1987 Aug;48(8):314-8
3611032
Health Educ Behav. 1998 Oct;25(5):613-24
9768381
Arch Intern Med. 2001 Jul 23;161(14):1703-8
11485502
J Biol Chem. 1995 Mar 31;270(13):7013-6
7706234
Ann Neurol. 2010 Mar;67(3):353-64
20373347
Arch Neurol. 2007 Mar;64(3):354-62
17353377
Fam Med. 1993 Jun;25(6):391-5
8349060
J Neurosci. 2005 Aug 24;25(34):7709-17
16120771
Brain. 2008 Mar;131(Pt 3):665-80
18263627
Lancet Neurol. 2006 Aug;5(8):655-60
16857570
Ann Neurol. 2008 Jan;63(1):112-8
18023012
Ann Neurol. 1999 Sep;46(3):412-6
10482274
J Am Geriatr Soc. 2004 Dec;52(12):2120-7
15571554
Neurology. 2003 Jun 24;60(12):1909-15
12821732
Exp Neurol. 2010 Jun;223(2):366-70
19664622
Brain. 2007 Nov;130(Pt 11):2837-44
17928318
Arch Neurol. 2010 Dec;67(12):1485-90
20697031
J Int Neuropsychol Soc. 2002 Mar;8(3):448-60
11939702
Neuroepidemiology. 2003 Jan-Feb;22(1):13-22
12566949
Neurobiol Aging. 2007 Feb;28(2):171-8
17097195
Neurobiol Aging. 2006 Jun;27(6):904-5
16638622
Neurology. 2009 Sep 15;73(11):847-53
19752451