Impact of APOE and BDNF Val66Met polymorphisms on spatial navigation and brain morphometry in subjective cognitive decline

Abstract

AbstractBackgroundThe apolipoprotein E (APOE) ɛ4 allele is associated with episodic memory deficits, less accurate spatial navigation and hippocampal atrophy in nondemented older adults. The brain‐derived neurotrophic factor (BDNF) Met allele may further worsen memory impairment and reduce hippocampal activation in APOE ɛ4 carriers but its role in APOE ɛ4‐related spatial navigation deficits has not been established. We aimed to evaluate the influence of combination of the APOE and BDNF Val66Met polymorphisms on spatial navigation, cognitive functions and volumes of selected brain regions associated with spatial navigation including the hippocampus, entorhinal cortex, precuneus, inferior parietal and posterior cingulate cortex in individuals with subjective cognitive decline (SCD).MethodIn total, 71 older adults with SCD from the Czech Brain Aging Study were stratified based on the APOE and BDNF Val66Met polymorphisms into four groups: ɛ4–/BDNF Val/Val (n =27), ɛ4–/BDNF Met (n = 15), ɛ4+/BDNF Val/Val (n =18), and ɛ4+/BDNF Met (n=11). 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.ResultThe ɛ4+/BDNF Met group, although similar to other polymorphism groups in age, gender, education, depressive symptoms and global cognitive function, had less accurate allocentric and allocentric delayed navigation performance than the ɛ4–/BDNFVal/Val group (p<0.05). There were no significant differences in egocentric navigation performance, cognitive performance in any cognitive domain including attention and working memory, nonverbal memory, executive function, language and visuospatial function and volumes of selected brain regions associated with spatial navigation between the polymorphism groups (p>0.05).ConclusionIndividuals with SCD and the high risk combination of APOE ɛ4 and BDNF Met alleles had less accurate allocentric spatial navigation than those with the low risk combination of APOE ɛ3 and BDNF Val alleles. This finding may indicate that individuals with SCD and two high risk gene polymorphisms are particularly susceptible to hippocampus‐dependent spatial navigation deficits and may be at greater risk of cognitive decline and progression to mild cognitive impairment. Our results also suggest that spatial navigation testing could more reliably assess the deleterious effect of the BDNF Met allele on cognition than other cognitive tests.