[P1–138]: DECLINE OF FUNCTIONAL INTERHEMISPHERIC CONNECTIVITY IN AGING: ASSOCIATION WITH PICALM GENOTYPE

Recent genome wide association studies identified a polymorphism in PICALM gene rs3851179 as a risk factor for AD (Harold et al., 2009; Lambert et al., 2009). The normal brain undergoes a substantial decrease of functional connections within resting-state networks during aging, but PICALM-related differences in functional connectivity remain unknown. The present study aimed to determine the possible PICALM genotype -related differences of the alterations of brain functional connectivity in normal aging. We examined PICALM genotype and age-related differences in resting state EEG relative power and functional connectivity assessed by interhemispheric EEG coherence in 145 non-demented volunteers (age range 20–80 years), subdivided into subgroups of those younger and older than 50 years of age and stratified by PICALM rs3851179 genotype. Informed written consent was obtained from all participants. All subjects underwent a neurological examination and cognitive screening. The significance of the differences between the EEG parameters in different groups was estimated using ANOVA in the GLM. The analysis was adjusted for ApoE genotype. Interhemispheric coherence of different EEG bands was found to decrease with age in all examined groups. The decline of interhemispheric alpha2 and beta coherence in aging was attenuated in the carriers of PICALM-A protective allele, whereas the homozygous presence of AD risk variant PICALM GG was associated with greater decline in interhemispheric coherence. The PICALM GG genotype was also associated with neurophysiological signs of hyperexcitability and cortical disinhibition, as described previously (Ponomareva et al., 2016). The reduction of alpha interhemispheric coherence of in elderly subjects correlated with the worse performance in verbal memory test. The results indicate that altered functional connectivity in normal aging is associated with PICALM genotype. The progressive decline in interhemispheric connectivity contributes to memory decrement and suggests the impact of age-related disconnection process in pathogenesis of AD in the carriers of PICALM GG genotype. Supported by Russian Science Foundation grant No 14–44–00077 (Aging-related genetic-EEG association study); in part by Russian Science Foundation grant No 14–15–01121 (genotyping of AD-gene), the grants from the Government of the Russian Federation (No14.B25.31.0033), and NIH/NIA AG029360, by RFBR grant No 15–04–08744-a.