Mapping the evolution of regional atrophy in Alzheimer's disease: Unbiased analysis of fluid-registered serial MRI

Abstract

Alzheimer's disease (AD) is characterized by progressive cerebral atrophy, which may be assessed by using volumetric MRI. We describe a voxel-based analysis of nonlinear-registered serial MRI to demonstrate the most statistically significant (P < 0.001) regions of change at different stages of the disease. We compared presymptomatic (n ‫؍‬ 4), mild (n ‫؍‬ 10), and moderately affected (n ‫؍‬ 12) patients with early-and late-onset AD, with age-and sexmatched controls, and demonstrated increasing global atrophy with advancing disease. Significantly increased rates of hippocampal atrophy were seen in presymptomatic and mildly affected patients. There was a shift in the distribution of temporal lobe atrophy with advancing disease; the inferolateral regions of the temporal lobes showed the most significantly increased rates of atrophy by the time the patients were mildly or moderately affected. Significantly increased rates of medial parietal lobe atrophy were seen at all stages, with frontal lobe involvement occurring later in the disease. Our results suggest that the sites showing the most significant rates of atrophy alter as the disease advances, and that regional atrophy is already occurring before the onset of symptoms. This technique provides insights into the natural history of AD, and may be a valuable tool in assessing the efficacy of disease-modifying treatments, especially if these treatments were to have region-specific effects.

Brain Mapping as a Tool to Study Neurodegeneration

“…[33][34][35][36] As expected, these differences are less profound between MCI and AD and between MCI and normal aging. Thus, in agreement with clinical observations that place MCI between normal cognitive aging and AD based on atrophy severity, MCI likewise appears to be intermediate between normal aging and AD.…”

Alzheimer Disease: Quantitative Structural Neuroimaging for Detection and Prediction of Clinical and Structural Changes in Mild Cognitive Impairment

“…Posterior cingulate and frontal atrophy have been inconsistently observed in MCI and mild AD in both cross-sectional and longitudinal studies (10,(14)(15)(16)(58)(59)(60)(61)(62). Methodological differences likely contribute to these discrepant findings.…”

Quantitative magnetic resonance techniques as surrogate markers of Alzheimer’s disease

“…Statistical parametric mapping (SPM) was used to compare the deformation computed by fluid registration in 10 people with mild AD and 12 people with moderate AD and four presymptomatic cases with a family history of autosomal dominant early onset AD who progressed to AD during the follow-up. 93 There was a regional variation in the rate of atrophy with increasing disease severity, which correlated with the pathologic progression of the disease. Increased rates of hippocampal and medial parietal lobe atrophy were identified in presymptomatic and mildly affected patients.…”