Brain-Derived Neurotrophic Factor Is Associated with Age-Related Decline in Hippocampal Volume

Abstract

Hippocampal volume shrinks in late adulthood, but the neuromolecular factors that trigger hippocampal decay in aging humans remains a matter of speculation. In rodents, brain-derived neurotrophic factor (BDNF) promotes the growth and proliferation of cells in the hippocampus and is important in long-term potentiation and memory formation. In humans, circulating levels of BDNF decline with advancing age, and a genetic polymorphism for BDNF has been related to gray matter volume loss in old age. In this study, we tested whether age-related reductions in serum levels of BDNF would be related to shrinkage of the hippocampus and memory deficits in older adults. Hippocampal volume was acquired by automated segmentation of magnetic resonance images in 142 older adults without dementia. The caudate nucleus was also segmented and examined in relation to levels of serum BDNF. Spatial memory was tested using a paradigm in which memory load was parametrically increased. We found that increasing age was associated with smaller hippocampal volumes, reduced levels of serum BDNF, and poorer memory performance. Lower levels of BDNF were associated with smaller hippocampi and poorer memory, even when controlling for the variation related to age. In an exploratory mediation analysis, hippocampal volume mediated the age-related decline in spatial memory and BDNF mediated the age-related decline in hippocampal volume. Caudate nucleus volume was unrelated to BDNF levels or spatial memory performance. Our results identify serum BDNF as a significant factor related to hippocampal shrinkage and memory decline in late adulthood.

Relationship Between Hippocampal Volume, Serum BDNF, and Depression Severity Following Electroconvulsive Therapy in Late-Life Depression

“…This could well be related to an age-related decrease in sBDNF levels. In our sample, the mean sBDNF level was 18.27 ng/ml, which is in line with earlier reports of elderly populations (Erickson et al, 2010;Bus et al, 2012;Rapinesi et al, 2015) but lower compared with levels ranging from 9.5 to 29.0 μg/ml in non-elderly depressed patients (Sen et al, 2008). Differences in the sBDNF level could also be explained by sample characteristics and protocols used (eg, urbanicity, sex, smoking status, time of blood withdrawal, and so on; Bus et al, 2011).…”

“…At baseline, higher sBDNF levels were associated with larger hippocampi, a result that was also shown by Erickson et al (2010) in 142 older adults without dementia and without depression.…”

“…Similar to pharmacological interventions, peripheral BDNF levels increase after ECT in some but not all studies (Polyakova et al, 2015). Moreover, there is strong evidence that decreased BDNF is associated with age-related hippocampal dysfunction and increased risk for depression (Erickson et al, 2010;Erickson et al, 2012).…”

Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice

“…*P < 0.05 vs. WT controls; # P < 0.05 vs. other hippocampal layers stages of AD (Peng et al 2005). Recent studies revealed that BDNF is associated with age-related decline in hippocampal volume (Erickson et al 2010) and prevents hippocampal atrophy in APP/PS1 mice Fig. 6 Analyses of amyloid plaque load and expression of Aβ metabolism enzymes in the hippocampus.…”

Age-related changes in cardiovascular system, autonomic functions, and levels of BDNF of healthy active males: role of yogic practice

“…Researchers suggested that aging might enhance basal norepinephrine level and depress heart rate variability (Shimazu et al 2005;Reardon and Malik 1996;Jensen-Ustad et al 1997). Brain-derived neurotropic factor (BDNF), a potent marker of adult neurogenesis and cognitive performance, declines with aging (Erickson et al 2010). Age-related changes in levels of cortisol, adrenocorticotropic hormone, dehydroepiandrosterone (DHEA) and of its sulfate (DHEAS), serotonin, and dopamine have been reported in literatures (Kuzina et al 2010;Garau et al 2006 andYonezawa et al 1989;Dreher et al 2008).…”