People with a first-degree family history of Alzheimer's disease are at an increased risk of developing dementia. Subjective memory impairment among individuals with no measurable cognitive deficits may also indicate elevated dementia risk. It remains unclear whether nondemented people with a positive family history of Alzheimer's disease are more likely to experience cognitive deficits and whether such an association reflects underlying neuropathology. We therefore investigated subjective memory impairment and hippocampal cortical thickness in 40 healthy older adults and 35 patients with amnestic mild cognitive impairment. We found greater subjective memory impairment and left hemispheric hippocampal cortical thinning associated with a first-degree family history of Alzheimer's disease in healthy older adults. This suggests that subjective memory impairment could reflect preclinical stage neurodegeneration among individuals with the family history risk factor.

A first-degree family history of Alzheimer's disease reflects genetic risks for the neurodegenerative disorder. Recent imaging data suggest localized effects of genetic risks on brain structure in healthy people. It is unknown whether this association can also be found in patients who already have dementia. Our aim was to investigate whether family history risk modulates regional medial temporal lobe cortical thickness in patients with Alzheimer's disease. We performed high-resolution magnetic resonance imaging and cortical unfolding data analysis on 54 patients and 53 nondemented individuals. A first-degree family history of Alzheimer's disease was associated with left hemispheric cortical thinning in the subiculum among patients and controls. The contribution of Alzheimer's disease family history to regional brain anatomy changes independent of cognitive impairment may reflect genetic risks that modulate onset and clinical course of the disease.