Dementia, quantitative neuroimaging, and apolipoprotein E genotype

Abstract

Background and purpose: Quantitative MR imaging differences in an elderly population of subjects with various clinical disorders (including dementia, particularly Alzheimer's disease and vascular dementia) and disorders of mild cognitive impairment were examined. Potential quantitative MR differences were assessed by presence or absence of the apolipoprotein E (APOE) epsilon4 allele and by level of cognitive deficit.

Methods: One hundred eighty subjects with a diagnosis of dementia or other clinical disorders were identified from an eligible population of 5,677 elderly individuals. Age, duration of disease, and head size (where appropriate) were considered as covariates. APOE genotype was determined by polymerase chain reaction using buccal material. Axial and coronal intermediate- and T2-weighted MR images were quantified using a multispectral segmentation algorithm. Cognitive status was assessed by means of a modified Mini-Mental Status Examination.

Results: All types of dementing illness showed significant volume reductions in the majority of structures examined, particularly in the total brain, hippocampus, and white and gray matter, and increased CSF and ventricular volumes. Subjects with mild cognitive impairment showed fewer atrophic changes but were still distinguishable from the 24 control subjects. Presence of an epsilon4 allele was associated with smaller hippocampal volume in subjects with Alzheimer's disease and vascular dementia within just 1 year of disease onset. For other analyses, atrophy related to the presence of the epsilon4 allele disappeared after controlling for age and length of disease.

Conclusion: The effects of the epsilon4 allele on brain morphology may be subtly expressed early in the development of dementia, but do not specifically affect cerebral atrophy thereafter. Cognitive impairment is associated with atrophy irrespective of diagnosis and presence of epsilon4.

fig 1.

A–C, Graphic depictions of mean (± SD) for brain volume (A), hippocampal volume (B), and VBR (C) for ϵ4+ and ϵ4− subjects for each diagnostic classification: control group, Alzheimer disease (AD), mild ambiguous (M/A), vascular dementia (VaD), cerebrovascular disease (CVA), frontal lobe dementia (FLA), Parkinson's disease (Parkinson), psychiatric disorder (Psych), dementia unknown (Dem Unk), alcoholism (ETOH), and amnesic disorder (Mem Amn). The first numeric value represents the total number of ϵ4− subjects, with the second numeric value indicating sample size of the ϵ4+ subjects

fig 2.

A–C, Scatter plots for subjects with AD and combined MCI and VaD by age for brain volume (A), hippocampal volume (B), and VBR (C) based on the following correlations: Brain volume, r_ϵ4− = −.26, P ≤ .01; r_ϵ4+ = −0.19, P ≤ .01; hippocampal volume, r_ϵ4− = 0.17, P ≤ .05; r_ϵ4+ = 0.01, P > .05; and VBR, r_ϵ4− = −.34, P ≤ .01; r_ϵ4+ = 0.13, P ≤ .05

fig 3.

A–C, Mean (± SD) for brain volume (A), hippocampal volume (B), and VBR (C) by length of disease (LOD) in years

fig 4.

A–C, Mean (± SD) for brain volume (A), hippocampal volume (B), and VBR (C) for 3MS performance, which has been segregated into three levels: normal (> 91), mild to moderate impairment (71–90), and moderate to severe impairment (<70). Correlation values (Spearman rank) for each brain measure by 3MS performance level are shown in the boxes