- Higher gene expression levels of brain-derived neurotrophic factor (BDNF) are linked to slower cognitive decline with aging and Alzheimer’s (AD) pathology.
- 535 older adults had annual cognitive testing until death and brain autopsy including dorsolateral prefrontal cortex measurement of BDNF gene expression.
- Before and after adjustment for age, sex, education, and neuropathology, higher brain BDNF was associated with slower cognitive decline (P< .001), with ~50% reduction in decline rate with 90th vs 10th percentile BDNF expression, and strongest association in dementia patients.
- BDNF was lower in persons with AD pathology (P=.006) but not associated with stroke, Lewy body disease, or hippocampal sclerosis.
- Effect of BDNF expression on cognitive decline in persons with AD pathology was strongest for high AD pathology levels (P=.015); for 90th percentile AD pathology, cognitive decline was ~40% slower with 90th vs 10th percentile BDNF expression.
- Brain tissue analysis requires biopsy or autopsy; BNDF should be studied in CSF or with imaging markers if feasible.
Why this matters
- BDNF may shed light on cognitive decline in aging and AD, hinting at underlying mechanisms, predictive markers, and therapeutic targets.