Abstract
Alzheimer’s disease (AD) is characterized by neurofibrillary tangle and neuropil thread deposition, which ultimately results in neuronal loss. A large number of magnetic resonance imaging studies have reported a smaller hippocampus in AD patients as compared to healthy elderlies. Even though this difference is often interpreted as atrophy, it is only an indirect measurement. A more direct way of measuring the atrophy is to use repeated MRIs within the same individual. Even though several groups have used this appropriate approach, the pattern of hippocampal atrophy still remains unclear and difficult to relate to underlying pathophysiology. Here, in this longitudinal study, we aimed to map hippocampal atrophy rates in patients with AD, mild cognitive impairment (MCI) and elderly controls. Data consisted of two MRI scans for each subject. The symmetric deformation field between the first and the second MRI was computed and mapped onto the three-dimensional hippocampal surface. The pattern of atrophy rate was similar in all three groups, but the rate was significantly higher in patients with AD than in control subjects. We also found higher atrophy rates in progressive MCI patients as compared to stable MCI, particularly in the antero-lateral portion of the right hippocampus. Importantly, the regions showing the highest atrophy rate correspond to those that were described to have the highest burden of tau deposition. Our results show that local hippocampal atrophy rate is a reliable biomarker of disease stage and progression and could also be considered as a method to objectively evaluate treatment effects.
Highlights
Alzheimer’s disease (AD) is the most common form of dementia in the elderly population [1]
The clinical diagnosis of AD requires that the patient has dementia [3], which is already associated with the widespread deposition of amyloid plaques and neurofibrillary tangles in the brain [4]
Hippocampal Volume Change We first examined the difference in hippocampal volume between MRI_acq1 and MRI_acq2
Summary
Alzheimer’s disease (AD) is the most common form of dementia in the elderly population [1]. More and more volumetric studies used longitudinal dataset and reported a higher rate of hippocampal volume loss in patients with AD than in elderly controls [11,12,13,14,15,16,17] global hippocampal volumetry is not always sensitive enough to follow changes within a single population [18], which may reflect conversion from healthy state or disease progression. These contradictory results ask for further research to find more precise methods to measure the hippocampal deformation during the progression of the disease
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