title: 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.
abstract: 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.
authors.affiliation: Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA. bradd@nmr.mgh.harvard.edu
authors.forename: Bradford C
authors.initials: BC
authors.lastname: Dickerson
authors.forename: Akram
authors.initials: A
authors.lastname: Bakkour
authors.forename: David H
authors.initials: DH
authors.lastname: Salat
authors.forename: Eric
authors.initials: E
authors.lastname: Feczko
authors.forename: Jenni
authors.initials: J
authors.lastname: Pacheco
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Greve
authors.forename: Fran
authors.initials: F
authors.lastname: Grodstein
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Wright
authors.forename: Deborah
authors.initials: D
authors.lastname: Blacker
authors.forename: H Diana
authors.initials: HD
authors.lastname: Rosas
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.forename: Alireza
authors.initials: A
authors.lastname: Atri
authors.forename: John H
authors.initials: JH
authors.lastname: Growdon
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: Bruce
authors.initials: B
authors.lastname: Fischl
authors.forename: Randy L
authors.initials: RL
authors.lastname: Buckner
mesh_terms: 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
chemical_list: D000682:Amyloid