BDNF Val66Met moderates the relationship between cardiorespiratory fitness and memory in cognitively normal older adults

Abstract

+61 8 9360 6193Keywords brain-derived neurotrophic factor, Val66Met, exercise, cardiorespiratory fitness, cognition, memory, physical activity Disclosure statementWe have no conflicts of interest to declare. AbstractHigher cardiorespiratory fitness has been associated with enhanced cognitive function in older adults; yet, this relationship demonstrates a degree of variability. Thus, it is hypothesised that variation in genetic factors may influence the relationship between fitness and cognitive health.In this study we evaluate whether the BDNF Val66Met polymorphism moderates the relationship between cardiorespiratory fitness and verbal and visuospatial memory. Data from ninety-nine cognitively normal men and women aged 60 -80 years were used. Fitness was assessed by peak oxygen consumption, and verbal and visuospatial memory were evaluated using well-validated measures. Participants were categorised into: lower-fit Met carriers, higher-fit Met carriers, lower-fit Val/Val, or higher-fit Val/Val. A significant interaction was observed between BDNF Val66Met and fitness on visuospatial memory performance; whereby lower-fit Met carriers performed 1SD lower than higher-fit Met carriers (p=0.04). We observed higher levels of fitness mitigated the deleterious effect of BDNF Met allele carriage on visuospatial memory. Future intervention studies should evaluate the effect of structured exercise on cognitive health between BDNF Val66Met carriers and Val/Val homozygotes.

Ketones: potential to achieve brain energy rescue and sustain cognitive health during ageing

“…without diet improve and maintain cognitive function in older adults at risk for AD (203,204) , potentially more than exercise alone (205) . While both physical activity (206) and nutritional ketogenic interventions (172) independently improve brain health and cognition, no RCTs have evaluated their combined effect on cognitive function in populations at risk of or living with cognitive decline. To the best of our knowledge, only a single case study using high-intensity interval training and KD along with cognitive training for 12 weeks in a 57-old woman with MCI has been published and reported a significant improvement in cognition (+8 points; MoCA) and biomarkers of the metabolic syndrome (207) .…”

“…Mitochondrial dysfunction and aberrant energy metabolism constitute critical factors in the pathogenesis of AD that could potentially be prevented or slowed down by combining these two therapeutic approaches. In addition to their effect on energy metabolism, exercise and ketogenic interventions share different adaptive responses in the brain that could contribute to cognitive health and resilience including neurogenesis, synaptic plasticity as well as protection against neuroinflammation, reactive oxygen species, and potentially proteotoxicity (206,229,230) . KD and exercise are also potent stimulators of monocarboxylate transporter expression, which are responsible for the passage of ketones across the blood-brain barrier (231,232) .…”

High-intensity Exercise and Cognitive Function in Cognitively Normal Older Adults: A Randomised Clinical Trial

“…Variability across studies might also be explained by factors moderating exercise-induced changes in cognition. Genetic factors, such as the apolipoprotein E (APOE) ε4 allele and the brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphism, may modulate the relationship between exercise and brain health (10)(11)(12). The literature in these elds is predominantly sourced from observational studies, which have contributed to largely inconsistent ndings.…”