The cortical signature of Alzheimer's disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals.
Alzheimer's disease (AD) is associated with neurodegeneration in vulnerable limbic and heteromodal regions of the cerebral cortex, detectable in vivo using magnetic resonance imaging. It is not clear whether abnormalities of cortical anatomy in AD can be reliably measured across different subject samples, how closely they track symptoms, and whether they are detectable prior to symptoms. An exploratory map of cortical thinning in mild AD was used to define regions of interest that were applied in a hypothesis-driven fashion to other subject samples. Results demonstrate a reliably quantifiable in vivo signature of abnormal cortical anatomy in AD, which parallels known regional vulnerability to AD neuropathology. Thinning in vulnerable cortical regions relates to symptom severity even in the earliest stages of clinical symptoms. Furthermore, subtle thinning is present in asymptomatic older controls with brain amyloid binding as detected with amyloid imaging. The reliability and clinical validity of AD-related cortical thinning suggests potential utility as an imaging biomarker. This "disease signature" approach to cortical morphometry, in which disease effects are mapped across the cortical mantle and then used to define ROIs for hypothesis-driven analyses, may provide a powerful methodological framework for studies of neuropsychiatric diseases.
Dickerson
Bradford C
BC
Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA. bradd@nmr.mgh.harvard.edu
Bakkour
Akram
A
Salat
David H
DH
Feczko
Eric
E
Pacheco
Jenni
J
Greve
Douglas N
DN
Grodstein
Fran
F
Wright
Christopher I
CI
Blacker
Deborah
D
Rosas
H Diana
HD
Sperling
Reisa A
RA
Atri
Alireza
A
Growdon
John H
JH
Hyman
Bradley T
BT
Morris
John C
JC
Fischl
Bruce
B
Buckner
Randy L
RL
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D000682:Amyloid / Q000096:biosynthesis*; D001931:Brain Mapping / Q000379:methods; D002540:Cerebral Cortex / Q000473:pathology*; D003704:Dementia / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000473:pathology; D012720:Severity of Illness Index
D000682:Amyloid