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Older adults with cognitive complaints show brain atrophy similar to that of amnestic MCI

From the Brain Imaging Laboratory, Departments of Psychiatry (A.J.S., H.A.W., L.A.R., R.B.S., L.A.F., J.D.W., T.L.M.) and Radiology (A.J.S., A.C.M.), Dartmouth Medical School, Hanover, NH.

Address correspondence and reprint requests to Dr. Andrew Saykin, Brain Imaging Laboratory, Department of Psychiatry, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756-0001; e-mail: andrew.saykin{at}dartmouth.edu

Objective: To examine the neural basis of cognitive complaints in healthy older adults in the absence of memory impairment and to determine whether there are medial temporal lobe (MTL) gray matter (GM) changes as reported in Alzheimer disease (AD) and amnestic mild cognitive impairment (MCI).

Methods: Participants were 40 euthymic individuals with cognitive complaints (CCs) who had normal neuropsychological test performance. The authors compared their structural brain MRI scans to those of 40 patients with amnestic MCI and 40 healthy controls (HCs) using voxel-based morphometry and hippocampal volume analysis.

Results: The CC and MCI groups showed similar patterns of decreased GM relative to the HC group on whole brain analysis, with differences evident in the MTL, frontotemporal, and other neocortical regions. The degree of GM loss was associated with extent of both memory complaints and performance deficits. Manually segmented hippocampal volumes, adjusted for age and intracranial volume, were significantly reduced only in the MCI group, with the CC group showing an intermediate level.

Conclusions: Cognitive complaints in older adults may indicate underlying neurodegenerative changes even when unaccompanied by deficits on formal testing. The cognitive complaint group may represent a pre–mild cognitive impairment stage and may provide an earlier therapeutic opportunity than mild cognitive impairment. MRI analysis approaches incorporating signal intensity may have greater sensitivity in early preclinical stages than volumetric methods.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the September 12 issue to find the title link for this article.

Supported in part by grants from the National Institute on Aging (R01 AG19771), Alzheimer's Association (Hedco Foundation), Hitchcock Foundation, Ira DeCamp Foundation, National Science Foundation, New Hampshire Hospital, and NAMIC (U54 EB005149).

Disclosure: The authors report no conflicts of interest.

Received August 13, 2005. Accepted in final form May 1, 2006.

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