Patterns of atrophy differ among specific subtypes of mild cognitive impairment.
BACKGROUND
In most patients, mild cognitive impairment (MCI) represents the clinically evident prodromal phase of dementia. This is most well established in amnestic MCI, which is most commonly a precursor to Alzheimer disease (AD). It follows, however, that subjects with MCI who have impairment in nonmemory domains may progress to non-AD degenerative dementias.


OBJECTIVE
To investigate patterns of cerebral atrophy associated with specific subtypes of MCI.


METHODS
Case-control study.


METHODS
Community-based sample at a tertiary referral center.


METHODS
One hundred forty-five subjects with MCI and 145 age- and sex-matched cognitively normal control subjects. Mild cognitive impairment was classified as amnestic, single cognitive domain; amnestic, multiple domain; nonamnestic, single domain; and nonamnestic, multiple domain. Subjects with nonamnestic single-domain MCI were classified into language, attention/executive, and visuospatial subgroups on the basis of specific cognitive impairment.


METHODS
Patterns of gray matter loss in the MCI groups compared with control subjects, assessed using voxel-based morphometry.


RESULTS
Subjects in the amnestic single- and multiple-domain groups showed loss in the medial and inferior temporal lobes compared with control subjects, and those in the multiple-domain group also had involvement of the posterior temporal lobe, parietal association cortex, and posterior cingulate. Subjects in the nonamnestic single-domain group with language impairment showed loss in the left anterior inferior temporal lobe. The group with attention/executive deficits showed loss in the basal forebrain and hypothalamus. No coherent patterns of loss were observed in the other subgroups.


CONCLUSIONS
The pattern of atrophy in the amnestic MCI groups is consistent with the concept that MCI in most of these subjects represents prodromal AD. However, the varying patterns in the language and attention/executive subgroups suggest that these subjects may have a different underlying disorder.
Whitwell
Jennifer L
JL
Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Petersen
Ronald C
RC
Negash
Selamawit
S
Weigand
Stephen D
SD
Kantarci
Kejal
K
Ivnik
Robert J
RJ
Knopman
David S
DS
Boeve
Bradley F
BF
Smith
Glenn E
GE
Jack
Clifford R
CR
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000209:etiology; D001288:Attention; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000139:chemically induced* / Q000145:classification* / Q000175:diagnosis / Q000523:psychology; D003704:Dementia / Q000209:etiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007802:Language; D008279:Magnetic Resonance Imaging; D008297:Male; D012720:Severity of Illness Index
Brain Res Rev. 2006 Aug;51(2):145-60
16530842
Arch Neurol. 2005 Sep;62(9):1393-7
16157746
Ann Neurol. 2000 Jan;47(1):36-45
10632099
Brain. 2000 Mar;123 Pt 3:484-98
10686172
Neuroimage. 2000 Jun;11(6 Pt 1):805-21
10860804
Ann Neurol. 2001 Apr;49(4):433-42
11310620
Arch Gen Psychiatry. 2002 Oct;59(10):946-51
12365882
Neuroreport. 2002 Oct 28;13(15):1939-43
12395096
Neurobiol Aging. 2003 Mar-Apr;24(2):197-211
12498954
Neurobiol Aging. 2003 Mar-Apr;24(2):221-31
12498956
J Intern Med. 2004 Sep;256(3):183-94
15324362
J Intern Med. 2004 Sep;256(3):240-6
15324367
Arch Neurol. 2004 Oct;61(10):1579-84
15477512
Neuroimage. 2004 Oct;23(2):708-16
15488420
J Psychiatr Res. 1975 Nov;12(3):189-98
1202204
Acta Neuropathol. 1991;82(4):239-59
1759558
J Neurosci. 1994 Jan;14(1):167-86
8283232
JAMA. 1995 Apr 26;273(16):1274-8
7646655
Lancet. 1996 Apr 20;347(9008):1091-5
8602063
Brain. 1996 Dec;119 ( Pt 6):2001-7
9010004
Ann Neurol. 1997 Jul;42(1):85-94
9225689
Neurology. 1997 Sep;49(3):786-94
9305341
Ann Neurol. 1998 Jul;44(1):134-8
9667603
J Clin Exp Neuropsychol. 1998 Apr;20(2):194-200
9777473
Neurology. 1998 Dec;51(6):1546-54
9855500
Neuroimage. 2005 Jun;26(2):600-8
15907317
N Engl J Med. 2005 Jun 9;352(23):2379-88
15829527
Arch Neurol. 2005 Jun;62(6):925-30
15956163
Arch Neurol. 2005 Jul;62(7):1160-3; discussion 1167
16009779
Neurology. 2006 Nov 28;67(10):1764-8
17130407