Cerebral atrophy, apolipoprotein E ɛ4, and rate of decline in everyday function among patients with amnestic mild cognitive impairment

Abstract 

Background

Patients with amnestic mild cognitive impairment (MCI) demonstrate decline in everyday function. In this study, we investigated whether whole brain atrophy and apolipoprotein E (APOE) genotype are associated with the rate of functional decline in MCI.

Methods

Participants were 164 healthy controls, 258 MCI patients, and 103 patients with mild Alzheimer's disease (AD), enrolled in the Alzheimer's Disease Neuroimaging Initiative. They underwent brain MRI scans, APOE genotyping, and completed up to six biannual Functional Activities Questionnaire (FAQ) assessments. Random effects regressions were used to examine trajectories of decline in FAQ across diagnostic groups, and to test the effects of ventricle-to-brain ratio (VBR) and APOE genotype on FAQ decline among MCI patients.

Results

Rate of decline in FAQ among MCI patients was intermediate between that of controls and mild AD patients. Patients with MCI who converted to mild AD declined faster than those who remained stable. Among MCI patients, increased VBR and possession of any APOE ɛ4 allele were associated with faster rate of decline in FAQ. In addition, there was a significant VBR by APOE ɛ4 interaction such that patients who were APOE ɛ4 positive and had increased atrophy experienced the fastest decline in FAQ.

Conclusions

Functional decline occurs in MCI, particularly among patients who progress to mild AD. Brain atrophy and APOE ɛ4 positivity are associated with such declines, and patients who have elevated brain atrophy and are APOE ɛ4 positive are at greatest risk of functional degradation. These findings highlight the value of genetic and volumetric MRI information as predictors of functional decline, and thus disease progression, in MCI.

Keywords: MRI, Brain atrophy, APOE ɛ4, Activities of daily living, MCI