Current concepts of mild cognitive impairment and their applicability to persons at-risk for familial Alzheimer's disease.
The definition of mild cognitive impairment (MCI) as a precursor for Alzheimer's disease (AD) represented an important step forward in diagnosing the illness in its earliest stage. However, diagnoses based principally on cognitive performance have limitations in that there is variability between centers in which tests are employed and in how they are interpreted. Advances in our understanding of imaging and biochemical changes occurring early in the illness have improved our ability to diagnose AD in this early phase and diagnostic criteria for AD have been proposed recently based on such biomarkers. Persons inheriting autosomal dominant mutations causing familial AD (FAD) are essentially certain to develop the disease. In our studies of preclinical persons at-risk for inheriting FAD, we applied MCI diagnostic criteria to carriers of FAD mutations to ascertain the extent to which they identified persons in the earliest stages of the clinical illness. Our results indicate the relative prevalence of MCI subtypes varies considerably depending on the tests used to measure cognition. Furthermore, we found that cognitive complaints in such persons were less predictive of mutation status than were informants' reports of cognitive loss. The study of FAD provides an opportunity to test various criteria for early AD and these observations should be taken into consideration in future iterations of such diagnostic criteria.
Ringman
John M
JM
Mary S. Easton Center for Alzheimer's Disease Research at UCLA, Associate Clinical Professor, UCLA Department of Neurology, 10911 Weyburn Ave., #200, Los Angeles, CA 90095-7226, USA. jringman@mednet.ucla.edu
Medina
Luis D
LD
Rodriguez-Agudelo
Yaneth
Y
Chavez
Mireya
M
Lu
Po
P
Cummings
Jeffrey L
JL
D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D003072:Cognition Disorders / Q000175:diagnosis* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D009483:Neuropsychological Tests; D053764:Presenilin-1 / Q000235:genetics; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000235:genetics; D012307:Risk Factors
D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1; D058255:Protease Nexins; D011956:Receptors, Cell Surface
Nat Med. 2007 Nov;13(11):1359-62
17934472
Arch Neurol. 1999 Mar;56(3):303-8
10190820
Dement Geriatr Cogn Disord. 2006;22(4):312-9
16940725
Neuropathology. 2000 Sep;20(3):239-45
11132942
Brain. 2000 Mar;123 Pt 3:484-98
10686172
Science. 1993 Aug 13;261(5123):921-3
8346443
J Neurol Neurosurg Psychiatry. 2004 Mar;75(3):500-2
14966176
Brain. 2007 Jul;130(Pt 7):1767-76
17522104
Neurosci Lett. 1995 Feb 15;186(1):17-20
7783942
Neurology. 2008 Jul 8;71(2):85-92
18509095
Int Psychogeriatr. 1997;9 Suppl 1:173-6; discussion 177-8
9447441
Neurology. 2005 Aug 23;65(4):552-8
16116115
N Engl J Med. 2005 Jun 9;352(23):2379-88
15829527
Neurology. 2000 Nov 28;55(10):1577-8
11094121
Neurology. 2006 Aug 8;67(3):467-73
16894109
Brain. 1997 Mar;120 ( Pt 3):491-501
9126060
Neurology. 2005 Jul 26;65(2):323-5
16043812
J Intern Med. 2004 Sep;256(3):183-94
15324362
Arch Neurol. 1991 Mar;48(3):278-81
2001185
J Neurol Sci. 2003 Dec 15;216(1):127-34
14607314
Neurology. 2006 Dec 26;67(12):2176-85
17190940
Lancet Neurol. 2007 Aug;6(8):734-46
17616482
Neurobiol Aging. 2009 May;30(5):682-90
17889968
Ann Neurol. 1994 Sep;36(3):368-78
8080245
Lancet Neurol. 2006 Oct;5(10):828-34
16987729
Psychol Assess. 2004 Dec;16(4):347-59
15584794
Arch Neurol. 1996 May;53(5):423-7
8624217
JAMA. 1995 Mar 22-29;273(12):942-7
7884953
Neurology. 2006 Mar 14;66(5):718-22
16534109
Am J Geriatr Psychiatry. 2004 Mar-Apr;12(2):146-56
15010344
Brain. 1998 Sep;121 ( Pt 9):1631-9
9762953
Clin Neuropsychol. 1999 Nov;13(4):537-42
10806467
N Engl J Med. 2006 Dec 21;355(25):2652-63
17182990
Neurology. 2001 May 8;56(9):1133-42
11342677
Neurology. 1984 Jul;34(7):939-44
6610841
J Neuropathol Exp Neurol. 2001 May;60(5):483-92
11379823
J Geriatr Psychiatry Neurol. 2005 Dec;18(4):228-33
16306245
Neurology. 2004 Oct 12;63(7):1175-80
15477534
J Int Neuropsychol Soc. 2001 Jul;7(5):631-9
11459114
Neurology. 1999 Apr 22;52(7):1397-403
10227624
Neurology. 2002 Nov 26;59(10):1594-9
12451203
Ann Neurol. 2004 Mar;55(3):306-19
14991808