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

Abstract

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.

Figure 1

Characterization of the healthy control (HC, n = 40), cognitive complaint (CC, n = 40), and mild cognitive impairment (MCI, n = 40) groups on verbal memory performance composite domain score and the Cognitive Complaint Index indicating the percentage of possible complaints. By definition, the HC group had normal memory performance and a low level of complaints, whereas the MCI group had significant complaints and deficits. The CC group had normal performance but was nearly as elevated in complaints as the MCI group.

Figure 2

Regions showing significant GM atrophy in the MCI and the CC groups compared to HC group. Displayed at the left of each panel are images showing selected regions with group differences in the overall analysis, including bilateral frontal (top), right hippocampus (middle), and left hippocampus (bottom, p < 0.001). Also displayed are graphs of group differences in signal intensity from spherical regions of interest in each of the corresponding brain areas. See text for full description of results of statistical analyses.

Figure 3

Verbal learning performance was positively related to gray matter density in left medial temporal regions across the entire sample (N = 120, p < 0.001). See text for a detailed description of the statistical analyses and results.

Figure 4

Higher levels of cognitive complaints were associated with decreased gray matter density in the left and right hippocampi across the entire sample (N = 120, p < 0.001). See text for a detailed description of the statistical analyses and results.

Figure 5

Hippocampal volume and gray matter density by group. Age- and intracranial volume–adjusted means (± SE) for manually segmented left and right hippocampi are shown in the top row. Age-adjusted gray matter densities for the hippocampi are shown in the bottom row.