Cognitive, genetic, and brain perfusion factors associated with four year incidence of Alzheimer's disease from mild cognitive impairment

Abstract

Background: There is a range of factors that predict the development of Alzheimer's disease (AD) dementia among patients with amnestic mild cognitive impairment (MCI).

Objectives: To identify the neuropsychological, genetic, and functional brain imaging data that best predict conversion to AD dementia in patients with amnestic MCI.

Methods: From an initial group of 42 amnestic MCI patients assessed with neurological, neuropsychological, and brain SPECT, 39 (25 converters, 14 non-converters) were followed for 4 years, and 36 had APOE ε4 genotyping. Baseline neuropsychological data and brain SPECT data were used to predict which of the MCI patients would develop dementia by the end of the 4 years of observation.

Results: The MCI patients who had converted to AD dementia had poorer performance on long-term visual memory and Semantic Fluency tests. The MCI subjects who developed dementia were more likely to carry at least one copy of the APOE ε4 allele (Hazard Risk = 4.22). There was lower brain perfusion in converters than non-converters, mainly in postcentral gyrus. An additional analysis of the SPECT data found differences between the MCI subjects and controls in the posterior cingulate gyrus and the basal forebrain. When the brain imaging and neuropsychological test data were combined in the same Cox regression model, only the neuropsychological test data were significantly associated with time to dementia.

Conclusion: Although the presence of reduced brain perfusion in postcentral gyrus and basal forebrain indicated an at-risk condition, it was the extent of memory impairment that was linked to the speed of decline from MCI to AD.

Keywords: Alzheimer's disease; brain SPECT; cerebral perfusion; four-year follow-up; longitudinal; mild cognitive impairment; prospective; visual memory.

Figure 1

Basal low blood flow on the right superior parieto-occipital lobe, right postcentral gyrus, left inferior frontal cortex, left superior parietal lobe, and bilateral precuneus associated with conversion to AD in amnestic MCI subjects. At the top, T-map was represented onto a glass brain in three orthogonal planes, called MIP (maximum intensity projection). At the bottom, T-map was superimposed on the canonical single-subject MR image of SPM8, for a better anatomical location. The colored scale represents statistical values (T-map), showing statistically significant lower brain perfusion in the converter MCI group than in the non converter MCI group (p< 0.01, extent threshold 30 voxels).

Figure 2

Regional perfusion defects (Controls > MCI > AD) The colored scale represents statistical values (T-map), showing statistically significant lower brain perfusion in the MCI and AD groups compared to the Control group.

Figure 3

Regions showing statistically significant correlation between baseline cerebral perfusion and performance on visual recall in all MCI subjects. The colored significant areas (X, Y, Z) are located in Brodman’s Areas 7, 9, 18 and 19 (right) and 11 (left).