The Combined Effect of APOE and BDNF Val66Met Polymorphisms on Spatial Navigation in Older Adults

BACKGROUND: The apolipoprotein E (APOE) ɛ4 allele is associated with episodic memory and spatial navigation deficits. The brain-derived neurotrophic factor (BDNF) Met allele may further worsen memory impairment in APOE ɛ4 carriers but its role in APOE ɛ4-related spatial navigation deficits has not been established. OBJECTIVE: We examined influence of APOE and BDNF Val66Met polymorphism combination on spatial navigation and volumes of selected navigation-related brain regions in cognitively unimpaired (CU) older adults and those with amnestic mild cognitive impairment (aMCI). METHODS: 187 participants (aMCI [n = 116] and CU [n = 71]) from the Czech Brain Aging Study were stratified based on APOE and BDNF Val66Met polymorphisms into four groups: ɛ4(–)/BDNF(Val/Val), ɛ4(–)/BDNF(Met), ɛ4(+)/BDNF(Val/Val), and ɛ4(+)/BDNF(Met). The participants underwent comprehensive neuropsychological examination, brain MRI, and spatial navigation testing of egocentric, allocentric, and allocentric delayed navigation in a real-space human analogue of the Morris water maze. RESULTS: Among the aMCI participants, the ɛ4(+)/BDNF(Met) group had the least accurate egocentric navigation performance (p < 0.05) and lower verbal memory performance than the ɛ4(–)/BDNF(Val/Val) group (p = 0.007). The ɛ4(+)/BDNF(Met) group had smaller hippocampal and entorhinal cortical volumes than the ɛ4(–)/BDNF(Val/Val) (p≤0.019) and ɛ4(–)/BDNF(Met) (p≤0.020) groups. Among the CU participants, the ɛ4(+)/BDNF(Met) group had less accurate allocentric and allocentric delayed navigation performance than the ɛ4(–)/BDNF(Val/Val) group (p < 0.05). CONCLUSION: The combination of APOE ɛ4 and BDNF Met polymorphisms is associated with more pronounced egocentric navigation impairment and atrophy of the medial temporal lobe regions in individuals with aMCI and less accurate allocentric navigation in CU older adults.