BDNF-Met polymorphism and amyloid-beta in relation to cognitive decline in cognitively normal elderly: the SCIENCe project

Karlijn A. van den Bosch, Inge M. W. Verberk*, Jarith L. Ebenau, Sven J. van der Lee, Iris E. Jansen, Niels D. Prins, Philip Scheltens, Charlotte E. Teunissen, Wiesje M. van der Flier

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Brain-derived neurotrophic factor (BNDF) plays a role in synapse integrity. We investigated in 398 cognitively normal adults (60±8years, 41% female, MMSE=28±1) the joint association of the Val66Met polymorphism of the BDNF gene (Met+/-) and plasma BDNF levels and abnormal cerebrospinal fluid (CSF) amyloid-beta status (A+/-) with cognitive decline and dementia risk. Age-, sex- and education-adjusted linear mixed models showed that compared to Met-A-, Met+A+ showed steeper decline on tests of global cognition, memory, language, attention and executive functioning, while Met-A+ showed steeper decline on a smaller number of tests. There were no associations between Met+A- and cognitive decline. Cox models showed that compared to Met-A-, Met+A+ participants were at increased risk of dementia (HR=8.8, 95%CI: 2.8–27.9), as were Met-A+ participants (HR=6.5, 95%CI: 2.2–19.5). Lower plasma BDNF was associated with an increased risk of progression to dementia in the A+ participants. Our results imply that Met-carriage on top of amyloid-beta pathology might increase rate of cognitive decline to dementia.
Original languageEnglish
Pages (from-to)146-154
Number of pages9
JournalNeurobiology of Aging
Publication statusPublished - 1 Dec 2021

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