Exercise and Alzheimer's disease biomarkers in cognitively normal older adults.
OBJECTIVE
In addition to the increasingly recognized role of physical exercise in maintaining cognition, exercise may influence Alzheimer's disease (AD) pathology, as transgenic mouse studies show lowered levels of AD pathology in exercise groups. The objective of this study was to elucidate the association between exercise and AD pathology in humans using Pittsburgh compound-B (PIB), amyloid-beta (Abeta)(42), tau, and phosphorylated tau (ptau)(181) biomarkers.


METHODS
Sixty-nine older adults (17 males, 52 females) aged 55 to 88 years, were recruited and confirmed to be cognitively normal. A questionnaire on physical exercise levels over the past decade was administered to all. Cerebrospinal fluid samples were collected from 56 participants, and amyloid imaging with PIB was performed on 54 participants.


RESULTS
Participants were classified based on biomarker levels. Those with elevated PIB (p = 0.030), tau (p = 0.040), and ptau(181) (p = 0.044) had significantly lower exercise, with a nonsignificant trend for lower Abeta(42) (p = 0.135) to be associated with less exercise. Results were similar for PIB after controlling for covariates; tau (p = 0.115) and ptau(181) (p = 0.123) differences were reduced to nonsignificant trends. Additional analyses also demonstrated that active individuals who met the exercise guidelines set by the American Heart Association had significantly lower PIB binding and higher Abeta(42) levels with and without controlling for covariates (PIB: p = 0.006 and p = 0.001; Abeta(42): p = 0.042 and p = 0.046). Last, the associations between exercise engagement and PIB levels were more prominent in APOE epsilon 4 noncarriers.


CONCLUSIONS
Collectively, these results are supportive of an association between exercise engagement and AD biomarkers in cognitively normal older adults.
Liang
Kelvin Y
KY
From the Program in Neuroscience, Division of Biology and Biomedical Sciences, Washington University, St. Louis, MO 63130, USA.
Mintun
Mark A
MA
Fagan
Anne M
AM
Goate
Alison M
AM
Bugg
Julie M
JM
Holtzman
David M
DM
Morris
John C
JC
Head
Denise
D
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000235:genetics / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D000814:Aniline Compounds; D001057:Apolipoproteins E / Q000235:genetics; D015444:Exercise / Q000502:physiology*; D005260:Female; D015577:Geriatric Assessment; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D049268:Positron-Emission Tomography / Q000379:methods; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D013844:Thiazoles; D016875:tau Proteins / Q000097:blood / Q000134:cerebrospinal fluid*
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D001057:Apolipoproteins E; D010446:Peptide Fragments; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
Neurobiol Learn Mem. 2007 Oct;88(3):277-94
17714960
Eur J Neurol. 2010 Jan;17(1):90-6
19659752
Ann Neurol. 2010 Jan;67(1):122-31
20186853
Biol Psychiatry. 2006 Dec 15;60(12):1314-23
16806094
J Neurol Neurosurg Psychiatry. 2009 Sep;80(9):966-75
19465413
J Neuropathol Exp Neurol. 1998 Dec;57(12):1168-74
9862640
Alzheimers Dement. 2009 Jul;5(4):287-94
19560099
Neurobiol Aging. 2011 Mar;32(3):506-14
19386382
Trends Genet. 2006 May;22(5):281-9
16567017
Alzheimer Dis Assoc Disord. 2009 Jul-Sep;23(3):188-97
19812458
Neurology. 1993 Nov;43(11):2412-4
8232972
Neuroreport. 2004 Aug 6;15(11):1751-4
15257141
Lancet Neurol. 2005 Nov;4(11):705-11
16239176
Med Sci Sports Exerc. 2007 Jan;39(1):199-207
17218903
Int J Mol Med. 2008 Oct;22(4):529-39
18813861
Alzheimers Dement. 2008 Jan;4(1):38-48
18631949
Neurobiol Aging. 2007 Jun;28(6):831-44
16730391
Med Sci Sports Exerc. 2000 Sep;32(9 Suppl):S498-504
10993420
J Neuropathol Exp Neurol. 2003 Dec;62(12):1220-7
14692698
Neurology. 2006 Aug 8;67(3):467-73
16894109
Cell. 2005 Mar 11;120(5):701-13
15766532
Clin Chem. 2005 Feb;51(2):336-45
15563479
Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6820-5
19346482
Ann Neurol. 2006 Mar;59(3):512-9
16372280
J Neurosci. 2005 Apr 27;25(17):4217-21
15858047
J Gerontol A Biol Sci Med Sci. 2006 Nov;61(11):1166-70
17167157
J Mol Neurosci. 2001 Oct;17(2):101-18
11816784
Am J Geriatr Pharmacother. 2009 Jun;7(3):167-85
19616185
Circulation. 2007 Aug 28;116(9):1094-105
17671236
Neurology. 2008 Jul 15;71(3):210-6
18625967
Am J Epidemiol. 2004 Aug 1;160(3):279-86
15258001
Alzheimers Dement. 2007 Apr;3(2 Suppl):S38-44
19595973
Biol Psychol. 2008 May;78(2):179-87
18395955
J Alzheimers Dis. 2007 Jun;11(3):359-70
17851186
Neurology. 2006 Aug 8;67(3):446-52
16894106
Am J Epidemiol. 2005 Apr 1;161(7):639-51
15781953
Arch Gen Psychiatry. 2009 Jan;66(1):81-7
19124691
Ann Neurol. 2009 Feb;65(2):176-83
19260027
Behav Brain Res. 2008 Jun 26;190(1):74-84
18342378
Arch Neurol. 2009 Dec;66(12):1476-81
20008651
J Neurosci Res. 2009 Aug 15;87(11):2561-70
19360903
Behav Brain Res. 2008 Sep 1;192(1):42-60
18468702
Nat Rev Neurosci. 2008 Jan;9(1):58-65
18094706
Arch Neurol. 2007 Mar;64(3):343-9
17210801
Ann Neurol. 2004 Mar;55(3):306-19
14991808