Structural brain changes in normal individuals with a maternal history of Alzheimer's

Abstract

Having a parent affected with late-onset Alzheimer's disease (LOAD) is a major risk factor for developing the disease among cognitively normal (NL) individuals. This magnetic resonance imaging (MRI) study examines whether NL with a LOAD-affected parent show preclinical brain atrophy, and whether there are parent-of-origin effects. Voxel-based morphometry (VBM) on Statistical parametric mapping (SPM8) was used to examine volumetric T1-MRI scans of 60 late-middle-aged NL subjects, divided into 3 size-matched, demographically balanced groups of 20 subjects each, including NL with a maternal (FHm), paternal (FHp), or negative family history (FH-) of LOAD. There were no group differences for clinical and neuropsychological measures, and ApoE status. On VBM, FHm showed reduced gray matter volumes (GMV) in frontal, parietal, and temporal cortices and precuneus as compared with FH-, and in precuneus compared with FHp (p < 0.05, family-wise error [FWE]-corrected). Results remained significant controlling for age, gender, education, ApoE, and total intracranial volume. No differences were observed between FHp and FH- in any regions. NL FHm showed reduced GMV in LOAD-affected brain regions compared with FH- and FHp, indicating higher risk for Alzheimer's disease. Our findings support the use of regional brain atrophy as a preclinical biomarker for LOAD among at-risk individuals.

Figure 1

Statistical parametric maps showing GMV reductions in NL FHm compared to FH- (in blue-green) and FHp (in violet), after correcting for total intracranial volume. Results are shown at P<0.05, FWE-corrected. a) Areas of GMV reductions are displayed onto the left and right lateral, superior and inferior views of a standardized, spatially normalized, 3D-rendered MRI. b) Areas of GMV reductions are displayed on coronal (1-3) and axial (4-7) slices of a standardized, spatially normalized MRI.

Figure 2

Quantitative GMV differences in FH groups. a. Percent difference in GMV in NL FHm vs FH- (in blue-green) and in FHm vs FHp (in violet) within the brain regions showing significant group effects at P<0.05, FWE-corrected, as depicted in Figure 1b and listed in Table 2. Areas of % difference in GMV across FH groups are displayed on axial (1-4) slices of a standardized, spatially normalized MRI. b. Selected volume parameter estimates from VBM analyses. The graphs show the corresponding parameter estimates for key regions identified in Figure 1 and listed in Table 2, representing group differences in GMV. Error bars are SEM. GMV was significantly reduced in NL FHm compared to both FHp and FH- in the precuneus (A), and compared to FH- in inferior parietal lobule (B), superior temporal gyrus (C) and inferior frontal gyrus (D).