How may brain MRI predict the development of Alzheimer’s disease?

 Presymptomatic cortical thinning in familial Alzheimer disease: a longitudinal MRI study

Weston PS, Nicholas JM, Lehmann M, et al.

Neurology 2016; 87:2050-2057.



To identify a cortical signature pattern of cortical thinning in familial Alzheimer disease (FAD) and assess its utility in detecting and tracking presymptomatic neurodegeneration.


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.


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.


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.

You may also check

The cortical signature of prodromal AD: regional thinning predicts mild AD dementia.

Bakkour A,Morris JC, Dickerson BC.

Neurology 2009; 72:1048–1055.

Both references are now included in the neurochecklist:

Alzheimer’s disease (AD): clinical features


Abstract link

By US National Institute on Aging, Alzheimer's Disease Education and Referral Center -, Public Domain, Link
By US National Institute on Aging, Alzheimer’s Disease Education and Referral Center –, Public Domain, Link

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