Longitudinal changes in hippocampal texture from healthy aging to Alzheimer's disease

Early detection of Alzheimer's disease is essential to develop preventive treatment strategies. Detectible change in brain volume emerges relatively late in the pathogenic progression of disease, but microstructural changes caused by early neuropathology may cause subtle changes in the MR signal, quantifiable using texture analysis. Texture analysis quantifies spatial patterns in an image, such as smoothness, randomness and heterogeneity. We investigated whether the MRI texture of the hippocampus, an early site of Alzheimer's disease pathology, is sensitive to changes in brain microstructure before the onset of cognitive impairment. We also explored the longitudinal trajectories of hippocampal texture across the Alzheimer's continuum in relation to hippocampal volume and other biomarkers. Finally, we assessed the ability of texture to predict future cognitive decline, over and above hippocampal volume. Data were acquired from the Alzheimer's Disease Neuroimaging Initiative. Texture was calculated for bilateral hippocampi on 3T T₁-weighted MRI scans. Two hundred and ninety-three texture features were reduced to five principal components that described 88% of total variance within cognitively unimpaired participants. We assessed cross-sectional differences in these texture components and hippocampal volume between four diagnostic groups: cognitively unimpaired amyloid-β^- (n = 406); cognitively unimpaired amyloid-β⁺ (n = 213); mild cognitive impairment amyloid-β⁺ (n = 347); and Alzheimer's disease dementia amyloid-β⁺ (n = 202). To assess longitudinal texture change across the Alzheimer's continuum, we used a multivariate mixed-effects spline model to calculate a 'disease time' for all timepoints based on amyloid PET and cognitive scores. This was used as a scale on which to compare the trajectories of biomarkers, including volume and texture of the hippocampus. The trajectories were modelled in a subset of the data: cognitively unimpaired amyloid-β^- (n = 345); cognitively unimpaired amyloid-β⁺ (n = 173); mild cognitive impairment amyloid-β⁺ (n = 301); and Alzheimer's disease dementia amyloid-β⁺ (n = 161). We identified a difference in texture component 4 at the earliest stage of Alzheimer's disease, between cognitively unimpaired amyloid-β^- and cognitively unimpaired amyloid-β⁺ older adults (Cohen's d = 0.23, P_adj = 0.014). Differences in additional texture components and hippocampal volume emerged later in the disease continuum alongside the onset of cognitive impairment (d = 0.30-1.22, P_adj < 0.002). Longitudinal modelling of the texture trajectories revealed that, while most elements of texture developed over the course of the disease, noise reduced sensitivity for tracking individual textural change over time. Critically, however, texture provided additional information than was provided by volume alone to more accurately predict future cognitive change (d = 0.32-0.63, P_adj < 0.0001). Our results support the use of texture as a measure of brain health, sensitive to Alzheimer's disease pathology, at a time when therapeutic intervention may be most effective.