Spatial navigation and verbal memory are influenced by the combined effects of APOE and BDNF Val66Met polymorphisms in mild cognitive impairment

Abstract

AbstractBackgroundThe apolipoprotein E (APOE) ɛ4 allele is associated with an increased risk of Alzheimer’s disease (AD), episodic memory deficits and less accurate spatial navigation in non‐demented older adults. The brain‐derived neurotrophic factor (BDNF) Val66Met polymorphism is also related to the increased risk of AD and more pronounced memory impairment but its role in APOE ɛ4‐related spatial navigation deficits has not been established. Our aim was to examine the influence of combination of APOE and BDNF Val66Met polymorphisms on spatial navigation and other cognitive functions in individuals with amnestic mild cognitive impairment (aMCI).MethodIn total, 116 older adults with aMCI from the Czech Brain Aging Study were stratified based on APOE and BDNF Val66Met polymorphisms into four groups: ɛ4–/BDNF Val/Val (n = 29), ɛ4–/BDNF Met (n = 11), ɛ4+/BDNF Val/Val (n = 52), and ɛ4+/BDNF Met (n = 24). All participants underwent comprehensive neuropsychological examination, brain MRI and spatial navigation testing of egocentric (body‐centred), allocentric (world‐centred), and allocentric delayed navigation in a real‐space human analogue of the Morris water maze.ResultThe ɛ4+/BDNF Met group although similar to other groups in age, gender, education, depressive symptoms and global cognitive function had less accurate egocentric navigation performance (ps ≤ .045). The differences in allocentric and allocentric delayed navigation performance were not significant (ps ≥ .651). The ɛ4+/BDNFMet group had lower verbal memory performance than the ɛ4–/BDNF Val/Val group (p = .007) and similar performance to the ɛ4–/BDNF Met (p = .071) and ɛ4+/BDNF Val/Val (p = .240) groups. There were no between‐group differences in other cognitive domains including attention and working memory, nonverbal memory, executive function, language and visuospatial function (ps ≥ .268).ConclusionThe aMCI carriers with the most risky combination of APOE ɛ4 and BDNF Met polymorphisms had more pronounced egocentric spatial navigation impairment than the other polymorphism groups and more pronounced memory deficits than the carriers with the least risky combination of APOE ɛ3 and BDNF Val/Val polymorphisms. These findings indicate that aMCI individuals with two risky gene polymorphisms are particularly susceptible to hippocampus‐dependent episodic memory deficits and even more to non‐hippocampus‐dependent egocentric spatial navigation impairment that may reflect more advanced underlying pathological changes.