Cognitive Reserve, Incident Cancer, and Rate of Memory Decline in Later Life

Abstract Cognitive reserve (cognitive skills and abilities acquired before onset of brain pathology) helps maintain cognitive function during aging. Cognitive decline after cancer treatment, known as “chemobrain,” is a prevalent outcome among older cancer survivors. It is unknown whether cognitive reserve buffers against acute neuropathological events such as cancer-related cognitive decline. We examined acute and long-term rate of memory decline associated with incident cancer diagnosis by education levels as proxy for cognitive reserve (low: <12 years; intermediate: 12 to <16 years; high: ≥16 years) in 14,449 adults aged 50+ in the US Health and Retirement Study from 1998-2016. Memory (z-scored) was assessed biennially as immediate and delayed word recall combined with proxy assessments. We used adjusted linear mixed models to determine long-term rates of memory decline before and after cancer diagnosis, and acute memory decline immediately after diagnosis (3,248 incident cases), and compared them with corresponding memory trajectories in cancer-free participants. Acute memory decline immediately after diagnosis was larger in those with low (-0.098 SD units, 95% CI: -0.150, -0.045) versus high (-0.038 SD units, 95% CI: -0.084, -0.008) education. Long-term memory decline after cancer was faster in those with low (-1.16 SD units/decade, 95% CI: -1.25, -1.07) versus high (-0.89 SD units/decade, 95% CI: -0.96, -0.82) education. Consistent with previous research showing an inverse cancer-dementia relationship, individuals with cancer had more favorable memory trajectories than cancer-free individuals with similar age and education. Among those with cancer, lower cognitive reserve was associated with greater acute and long-term memory decline after diagnosis.