Subregional hippocampal atrophy predicts Alzheimer's dementia in the cognitively normal

Atrophic changes of the hippocampus are typically regarded as an early sign of Alzheimer's dementia (AD). Using the radial distance atrophy mapping approach, we compared the longitudinal MRI data of 10 cognitively normal elderly subjects who remained normal at 3-year and 6-year follow-up (NL-NL) and 7 cognitively normal elderly subjects who were diagnosed with mild cognitive impairment (MCI) 2.8 (range 2.0–3.9) and with AD 6.8 years (range 6.1–8.2) after baseline (NL-MCIAD). 3D statistical maps revealed greater hippocampal atrophy in the NL-MCIAD relative to the NL-NL group at baseline (left p = 0.05; right p = 0.06) corresponding to 10–15% CA1, and 10–25% subicular atrophy, and bilateral differences at 3-year follow-up (left p = 0.001, right p < 0.02) corresponding to 10–30% subicular, 10–20% CA1, and 10–20% newly developed CA2-3 atrophy. This preliminary study suggests that excess CA1 and subicular atrophy is present in cognitively normal individuals predestined to decline to amnestic MCI, while progressive involvement of the CA1 and subiculum, and atrophy spreading to the CA2-3 subfield in amnestic MCI, suggests future diagnosis of AD.