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. 2017;59(4):1269-1282.
doi: 10.3233/JAD-170286.

The Relationship of Brain Amyloid Load and APOE Status to Regional Cortical Thinning and Cognition in the ADNI Cohort

Chunfei Li  1 , David A Loewenstein  2   3   4 , Ranjan Duara  2   4   5 , Mercedes Cabrerizo  1 , Warren Barker  2   5 , Malek Adjouadi  1   5 ; Alzheimer’s Disease Neuroimaging Initiative
Affiliations

The Relationship of Brain Amyloid Load and APOE Status to Regional Cortical Thinning and Cognition in the ADNI Cohort

Chunfei Li et al. J Alzheimers Dis. 2017.

Abstract

Background: Both amyloid (Aβ) load and APOE4 allele are associated with neurodegenerative changes in Alzheimer's disease (AD) prone regions and with risk for cognitive impairment.

Objective: To evaluate the unique and independent contribution of APOE4 allele status (E4+∖E4-), Aβ status (Amy+∖Amy-), and combined APOE4 and Aβ status on regional cortical thickness (CoTh) and cognition among participants diagnosed as cognitively normal (CN, n = 251), early mild cognitive impairment (EMCI, n = 207), late mild cognitive impairment (LMCI, n = 196), and mild AD (n = 162) from the ADNI.

Methods: A series of two-way ANCOVAs with post-hoc Tukey HSD tests, controlling independently for Aβ and APOE4 status and age were examined.

Results: Among LMCI and AD participants, cortical thinning was widespread in association with Amy+ status, whereas in association with E4+ status only in the inferior temporal and medial orbito-frontal regions. Among CN and EMCI participants, E4+ status, but not Amy+ status, was independently associated with increased CoTh, especially in limbic regions [e.g., in the entorhinal cortex, CoTh was 0.123 mm greater (p = 0.002) among E4+ than E4-participants]. Among CN and EMCI, both E4+ and Amy+ status were independently associated with cognitive impairment, which was greatest among those with combined E4 + and Amy+ status.

Conclusion: Decreased CoTh is independently associated with Amy+ status in many brain regions, but with E4+ status in very restricted number of brain regions. Among CN and EMCI participants, E4 + status is associated with increased CoTh, in medial and inferior temporal regions, although cognitive impairment at this state is independently associated with Amy+ and E4 + status. These findings imply a unique pathophysiological mechanism for E4 + status in AD and its progression.

Keywords: ADNI; APOE; Alzheimer’s disease; amyloid; cortical thinning; memory; mild cognitive impairment.

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Figures

Fig. 1.
Fig. 1.
Differences in mean amyloid load (18F-AV45) SUVR for each diagnostic group between E4− and E4+ participants.
Fig. 2.
Fig. 2.
Barplot of CoTh among Amy− and Amy+ participants in 4 diagnostic groups for 12 brain regions.
Fig. 3.
Fig. 3.
Barplot of CoTh among E4− and E4+ participants in 4 diagnostic groups for 12 brain regions.
Fig. 4.
Fig. 4.
Bar graph of scores on following cognitive tests: MMSE, RAVLT (immediate), RAVLT (% forgetting) and ADAS13. Individual bars represent the following groups of participants: E4−/Amy−; E4+/Amy−; E4−/Amy+ and E4+/Amy+. The colored asterisk (*p <0.05; **p <0.01; ***p <0.001) on the E4−/Amy− indicates a significant difference in score from the score for the corresponding color bar, i.e., E4+/Amy+ group, same as E4−/Amy+ bars in RAVLT (immediate) and ADAS13, as well as E4+/Amy− in ADAS13. There was no significant difference among E4−/Amy−, E4+/Amy−, E4−/Amy+ group.
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