The BDNF Val66Met polymorphism moderates the relationship between cognitive reserve and executive function

Abstract

The concept of cognitive reserve (CR) has been proposed to account for observed discrepancies between pathology and its clinical manifestation due to underlying differences in brain structure and function. In 433 healthy older adults participating in the Tasmanian Healthy Brain Project, we investigated whether common polymorphic variations in apolipoprotein E (APOE) or brain-derived neurotrophic factor (BDNF) influenced the association between CR contributors and cognitive function in older adults. We show that BDNF Val66Met moderates the association between CR and executive function. CR accounted for 8.5% of the variance in executive function in BDNF Val homozygotes, but CR was a nonsignificant predictor in BDNF Met carriers. APOE polymorphisms were not linked to the influence of CR on cognitive function. This result implicates BDNF in having an important role in capacity for building or accessing CR.

Relationship betweenAPOEGenotype and Structural MRI Measures throughout Adulthood in the Study of Health in Pomerania Population-Based Cohort

“…The results on cognitive reserve and APOE are controversial in the literature. However APOE does not seem to modulate the effect of cognitive reserve on cognitive function 35 . Due to the lack of functional imaging measures in our cohort we could not evaluate the presence of these changes in the framework of SHIP.…”

Impact of brain‐derived neurotrophic factor genetic polymorphism on cognition: A systematic review

“…A total of 23 studies evaluated the association between the BDNF polymorphism and the attention/concentration domain (Alfimova et al., ; Cherubin et al., ; da Rocha, Malloy‐Diniz, Lage, & Correa, ; Dennis et al., ; Freundlieb et al., ; Freundlieb et al., ; Gatt et al., ; Ho et al., ; Huang et al., ; Kim et al., ; Lim et al., ; Lin et al., ; Mezquida et al., ; Narayanan et al., ; Oroszi et al., ; Schofield et al., ; Swardfager et al., ; Szabo et al., ; Thow, Summers, Summers, Saunders, & Vickers, ; Tukel et al., ; Ward et al., ; Yu et al., ; Zhang et al., ). Ten of these studies focused on healthy subjects (Alfimova et al., ; Cherubin et al., ; Dennis et al., ; Freundlieb et al., , ; Gatt et al., ; Huang et al., ; Lim et al., ; Schofield et al., ; Ward et al., ), and the rest evaluated samples of different disease states such as Alzheimer’s disease ( n = 1) (Lin et al., ), cardiovascular diseases ( n = 2) (Swardfager et al., ; Szabo et al., ), obsessive‐compulsive disorder ( n = 2) (da Rocha et al., ; Tukel et al., ), schizophrenia ( n = 5) (Ho et al., ; Kim et al., ; Mezquida et al., ; Zhang et al., , ), traumatic brain injury ( n = 2) (Narayanan et al., ; Yu et al., ), and systemic lupus erythematous ( n = 1) (Oroszi et al., ).…”

“…Forty‐seven relevant studies were identified within the executive function domain. Twenty studies evaluated on healthy subjects (Alfimova et al., ; Cherubin et al., ; Dennis et al., ; De Beaumont et al., ; Erickson et al., ; Freundlieb et al., ; Freundlieb et al., ; Gong et al., ; Gajewski et al., ; Ghisletta et al., ; Gonzalez et al., ; Harris et al., ; Huang et al., ; Lim et al., ; Schofield et al., ; Thibeau, McFall, Wiebe, Anstey, & Dixon, ; Thow et al., ; Ward et al., , ; Wilkosc et al., ), and the rest evaluated samples of different disease states such as Alzheimer’s disease ( n = 4) (Lee et al., ; Lin et al., ; Nagata et al., , ), Parkinson’s disease ( n = 3) (Altmann et al., ; Bialecka et al., ; van der Kolk et al., ), cardiovascular diseases ( n = 2) (Swardfager et al., ; Szabo et al., ), obsessive‐compulsive disorder ( n = 2) (da Rocha et al., ; Tukel et al., ), schizophrenia and bipolar disorder ( n = 7) (Egan et al., ; Ho et al., ; Kim et al., ; Lee et al., ; Mezquida et al., ; Rybakowski et al., , ), traumatic brain injury ( n = 4) (Barbey et al., ; McAllister et al., ; Narayanan et al., ; Yu et al., ), depression ( n = 1) (Yin et al., ), multiple sclerosis ( n = 1) (Fera et al., ), breast cancer patients ( n = 1) (Ng et al., ), systemic lupus erythematosus ( n = 1) (Oroszi et al., ), and psychosis ( n = 1) (Aas et al., ).…”

“…Eighteen studies were identified when evaluating BDNF Val66Met polymorphism within the verbal fluency domain. These studies evaluated populations of different disease states such as healthy controls ( n = 11) (Alfimova et al., ; De Beaumont et al., ; Gajewski et al., ; Gong et al., ; Freundlieb et al., , ; Harris et al., ; Huang et al., ; Karnik, Wang, Barch, Morris, & Csernansky, ; Schofield et al., ; Ward et al., ), traumatic brain injury ( n = 1) (Yu et al., ), obsessive‐compulsive disorder ( n = 1) (Tukel et al., ), psychosis ( n = 2) (Aas et al., ; Martinho et al., ), Parkinson’s disease ( n = 1) (van der Kolk et al., ), cardiovascular diseases ( n = 1) (Szabo et al., ), and breast cancer patients ( n = 1) (Ng et al., ). In all 18 of the identified studies, none of the studies observed an association between the BDNF Val66Met polymorphism and verbal fluency domain.…”

Genetic epistasis regulates amyloid deposition in resilient aging

“…By combining layers of genetic, transcriptomic, and neuroimaging data, we have shown that BDNF Val66Met status may determine the background on which SORL1 risk variants exert their effects (results across phenotypes are summarized in Table S1). Through this lens, BDNF’s modulation of resilience via cognitive reserve [32] is also clarified; depending on SORL1 genotype, the effects of Val66Met may influence protection against AD by promoting diffuse plaque deposition preferentially over neuritic.…”