Olfactory impairment in presymptomatic Alzheimer's disease.
Alzheimer's disease (AD) impairs olfaction, but it is uncertain how early this occurs in the disease process and whether the effect can be accounted for by other behavioral or genetic markers of the disease. We administered the Brief Smell Identification Test (BSIT) to 471 older people without dementia or cognitive impairment who then completed annual clinical evaluations and brain autopsy at death. BSIT score was associated with more rapid decline in episodic memory and with increased risk of developing incident mild cognitive impairment (MCI), even after controlling for baseline level of episodic memory and possession of an apolipoprotein E epsilon4 allele. In 34 people who died without evidence of cognitive impairment, lower BSIT score was associated with higher level of AD pathology, even after controlling for epsilon4 and for level of episodic memory function when olfaction was assessed. These analyses suggest that among older people without clinical manifestations of AD or MCI, olfactory dysfunction is related to both the level of AD pathology in the brain and the risk of subsequently developing prodromal symptoms of the disease, and that these associations persist after accounting for the effects of other recognized behavioral and genetic markers of the disease.
Wilson
Robert S
RS
Department of Neurological Sciences, Rush Alzheimer's Disease Center, Rush University Medical Cetner, Chicago, Illinois 60612, USA. rwilson@rush.edu
Arnold
Steven E
SE
Schneider
Julie A
JA
Boyle
Patricia A
PA
Buchman
Aron S
AS
Bennett
David A
DA
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D053327:Apolipoprotein E4 / Q000235:genetics; D003072:Cognition Disorders / Q000235:genetics / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D009812:Odorants; D000857:Olfaction Disorders / Q000235:genetics / Q000503:physiopathology*
D053327:Apolipoprotein E4
J Int Neuropsychol Soc. 2005 Jul;11(4):400-7
16209420
Neuropsychology. 1999 Jan;13(1):47-53
10067775
Hippocampus. 1991 Jan;1(1):1-8
1669339
Science. 1984 Sep 14;225(4667):1168-70
6474172
Neurobiol Aging. 2008 May;29(5):693-706
17207898
Neurology. 2002 Jul 23;59(2):198-205
12136057
Neuroepidemiology. 2006;27(3):143-53
16974109
Lancet. 1997 Jun 21;349(9068):1793-6
9269213
J Clin Exp Neuropsychol. 2004 Sep;26(6):779-94
15370375
Neurobiol Aging. 2003 Jul-Aug;24(4):521-36
12714109
J Clin Exp Neuropsychol. 2003 Aug;25(5):634-42
12815501
Physiol Behav. 1984 Mar;32(3):489-502
6463130
J Lipid Res. 1990 Mar;31(3):545-8
2341813
Neurology. 2005 Mar 8;64(5):834-41
15753419
Ann N Y Acad Sci. 1998 Nov 30;855:744-50
9929680
Am J Psychiatry. 1991 Mar;148(3):357-60
1992839
Neurobiol Aging. 1991 Jul-Aug;12(4):295-312
1961359
Neurology. 2008 Sep 16;71(12):888-95
18794491
J Neurol Neurosurg Psychiatry. 2002 Dec;73(6):672-7
12438469
Arch Gen Psychiatry. 2007 Jul;64(7):802-8
17606814
Clin Neurol Neurosurg. 2005 Apr;107(3):165-73
15823670
Biometrics. 1982 Dec;38(4):963-74
7168798
Neurol Sci. 2005 Jul;26(3):156-60
16086128
Neuroepidemiology. 2005;25(4):163-75
16103727
Arch Neurol. 1998 Jan;55(1):84-90
9443714
Chem Senses. 2001 May;26(4):409-17
11369675
Neurology. 1984 Jul;34(7):939-44
6610841
Neurology. 2006 Jun 27;66(12):1837-44
16801647
Stat Med. 2000 Jun 15-30;19(11-12):1555-66
10844718
Neurobiol Aging. 1990 Jul-Aug;11(4):465-9
2381506
Am J Psychiatry. 2003 Nov;160(11):1995-2002
14594747
Ir J Med Sci. 2005 Oct-Dec;174(4):46-50
16445161
Brain Res Bull. 1987 May;18(5):597-600
3607528
Arch Neurol. 2002 Jul;59(7):1154-60
12117364
J Neurol Neurosurg Psychiatry. 2007 Jan;78(1):30-5
17012338
Neurosci Biobehav Rev. 2002 Nov;26(7):777-83
12470689
Brain Res Bull. 2003 Aug 15;61(3):235-42
12909293
Brain Res. 2002 Sep 27;951(1):77-81
12231459