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Updated: Sep 6, 2025

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Published on: April 23, 2021
BDNF Val66Met Moderates the Effects of Hypertension on Executive Functioning in Older Adults Diagnosed With aMCI
Peter Louras1, Lisa M Brown2, Rowena Gomez3
1Sierra Pacific Mental Illness Research (PL, JKF), Education, and Clinical Center (MIRECC) at VA Palo Alto Health Care System, Palo Alto, CA; Department of Psychiatry and Behavioral Sciences (PL, LMB, JKF), Stanford University School of Medicine, Stanford, CA.
Objective:
To investigate whether the BDNF Val66Met polymorphism influences the associations of hypertension, executive functioning and processing speed in older adults diagnosed with amnestic Mild Cognitive Impairment (aMCI).
Design:
Secondary data analysis using moderation modeling.
Setting:
Veterans Affairs Hospital, Palo Alto, CA.
Participants:
Sample included 108 community-dwelling volunteers (mean age 71.3 ± 9.2 years) diagnosed with aMCI.
Measurements:
Cognitive performance was evaluated from multiple baseline assessments (Trail Making Test; Stroop Color-Word Test; Symbol Digit Modality Test) and grouped into standardized composite scores representing executive function and processing speed domains. BDNF genotypes were determined from whole blood samples. Hypertension was assessed from resting blood pressures or by self-report.
Results:
Controlling for age, BDNF Val66Met moderated the effects of hypertension on executive functioning, but added no significant variance to processing speed scores. Specifically, hypertensive carriers of the BDNF Met allele performed significantly below the sample mean on tasks of executive functioning, and evidenced significantly lower scores when compared to Val-Val homozygotes and normotensive participants.
Conclusions:
Results posit that the executive functioning of non-demented older adults may be susceptible to interactions between BDNF genotype and hypertension, and Val-Val homozygotes and normotensive older adults may be more resilient to these effects of cognitive change. Further research is needed to understand the underlying processes and to implement strategies that target modifiable risk factors and promote cognitive resilience.
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