Weston, PS;
Nicholas, JM;
Lehmann, M;
Ryan, NS;
Liang, Y;
Macpherson, K;
Modat, M;
... Fox, NC; + view all
(2016)
Presymptomatic cortical thinning in familial Alzheimer disease: A longitudinal MRI study.
Neurology
, 87
(19)
pp. 2050-2057.
10.1212/WNL.0000000000003322.
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Abstract
OBJECTIVE: To identify a cortical signature pattern of cortical thinning in familial Alzheimer disease (FAD) and assess its utility in detecting and tracking presymptomatic neurodegeneration. METHODS: We recruited 43 FAD mutation carriers-36 PSEN1, 7 APP (20 symptomatic, 23 presymptomatic)-and 42 healthy controls to a longitudinal clinical and MRI study. T1-weighted MRI scans were acquired at baseline in all participants; 55 individuals (33 mutation carriers; 22 controls) had multiple (mean 2.9) follow-up scans approximately annually. Cortical thickness was measured using FreeSurfer. A cortical thinning signature was identified from symptomatic FAD participants. We then examined cortical thickness changes in this signature region in presymptomatic carriers and assessed associations with cognitive performance. RESULTS: The cortical signature included 6 regions: entorhinal cortex, inferior parietal cortex, precuneus, superior parietal cortex, superior frontal cortex, and supramarginal gyrus. There were significant differences in mean cortical signature thickness between mutation carriers and controls 3 years before predicted symptom onset. The earliest significant difference in a single region, detectable 4 years preonset, was in the precuneus. Rate of change in cortical thickness became significantly different in the cortical signature at 5 years before predicted onset, and in the precuneus at 8 years preonset. Baseline mean signature thickness predicted rate of subsequent thinning and correlated with presymptomatic cognitive change. CONCLUSIONS: The FAD cortical signature appears to be similar to that described for sporadic AD. All component regions showed significant presymptomatic thinning. A composite signature may provide more robust results than a single region and have utility as an outcome measure in presymptomatic trials.
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