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Jennifer L. Whitwell, PhD; Ronald C. Petersen, MD; Selamawit Negash, PhD; Stephen D. Weigand, MS; Kejal Kantarci, MD; Robert J. Ivnik, PhD; David S. Knopman, MD; Bradley F. Boeve, MD; Glenn E. Smith, PhD; Clifford R. Jack Jr, MD

Arch Neurol. 2007;64(8):1130-1138.

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.

Design  Case-control study.

Setting  Community-based sample at a tertiary referral center.

Patients  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.

Main Outcome Measure  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.

Author Affiliations: Departments of Radiology (Drs Whitwell, Kantarci, and Jack), Behavioral Neurology (Drs Petersen, Negash, Knopman, and Boeve), Biostatistics (Mr Weigand), and Psychiatry and Psychology (Drs Ivnik and Smith), Mayo Clinic, Rochester, Minnesota.

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