The effect of age and smoking on the hippocampus and memory in late middle age

From middle age the hippocampus atrophies at an accelerating rate. Factors that further this acceleration may hasten memory decline and the onset of memory disorder. We studied associations between smoking history, age, ApoE e4 genotype, vascular risk factors, hippocampal volume, and cognition in 67 middle-aged subjects (mean age = 56 years) who were offspring of parents with dementia. Subjects underwent isotropic T1-weighted 3 T MRI brain scanning with FreeSurfer volumetric data extraction for the hippocampus, a neuropsychological assessment battery, extensive medical data collection, and ApoE genotyping. ApoE e4, vascular risk variables, and alcohol history were unrelated to hippocampal volume. Hippocampal volume correlated negatively with age and positively with memory performance, but not with global cognition. Aging diminished hippocampal volume by 0.52% per year. Female subjects (only two males smoked) with a heavy smoking history (≥ 9.5 pack-years; n = 11) exhibited hippocampal volumes that were 7.4% smaller than the volumes of females (n = 37) with a light or no smoking history. In our sample by late middle age, a history of moderate to heavy smoking is associated with hippocampal atrophy equivalent to 12 years of aging. Since only a small number of subjects within the sample have a smoking history, validation of this finding in larger samples is desirable.