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Brain imaging of cognitively normal individuals with 2 parents affected by late-onset AD.

TitleBrain imaging of cognitively normal individuals with 2 parents affected by late-onset AD.
Publication TypeJournal Article
Year of Publication2014
AuthorsMosconi L, Murray J, Tsui WH, Li Y, Spector N, Goldowsky A, Williams S, Osorio R, McHugh P, Glodzik L, Vallabhajosula S, de Leon MJ
JournalNeurology
Volume82
Issue9
Pagination752-60
Date Published2014 Mar 04
ISSN1526-632X
KeywordsAdult, Aged, Alzheimer Disease, Atrophy, Brain, Brain Mapping, Child of Impaired Parents, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Radionuclide Imaging
Abstract

OBJECTIVES: This brain imaging study examines whether cognitively normal (NL) individuals with 2 parents affected by late-onset Alzheimer disease (LOAD) show evidence of more extensive Alzheimer disease pathology compared with those who have a single parent affected by LOAD.

METHODS: Fifty-two NL individuals received MRI, (11)C-Pittsburgh compound B (PiB)-PET, and (18)F-fluoro-2-deoxyglucose (FDG)-PET. These included 4 demographically balanced groups (n = 13/group, aged 32-72 years, 60% female, 30% APOE ε4 carriers) of NL individuals with maternal (FHm), paternal (FHp), and maternal and paternal (FHmp) family history of LOAD, and with negative family history (FH-). Statistical parametric mapping, voxel-based morphometry, and z-score mapping were used to compare MRI gray matter volumes (GMVs), partial volume-corrected PiB retention, and FDG metabolism across FH groups and vs FH-.

RESULTS: NL FHmp showed more severe abnormalities in all 3 biomarkers vs the other groups regarding the number of regions affected and magnitude of impairment. PiB retention and hypometabolism were most pronounced in FHmp, intermediate in FHm, and lowest in FHp and FH-. GMV reductions were highest in FHmp and intermediate in FHm and FHp vs FH-. In all FH+ groups, amyloid-β deposition exceeded GMV loss and hypometabolism exceeded GMV loss (p < 0.001), while amyloid-β deposition exceeded hypometabolism in FHmp and FHp but not in FHm.

CONCLUSIONS: These biomarker findings show a "LOAD parent-dose effect" in NL individuals several years, if not decades, before possible clinical symptoms.

DOI10.1212/WNL.0000000000000181
Alternate JournalNeurology
PubMed ID24523481
PubMed Central IDPMC3945651
Grant ListR01 AG022374 / AG / NIA NIH HHS / United States
R01 AG035137 / AG / NIA NIH HHS / United States
AG035137 / AG / NIA NIH HHS / United States
R01 AG013616 / AG / NIA NIH HHS / United States
P30 AG008051 / AG / NIA NIH HHS / United States
AG022374 / AG / NIA NIH HHS / United States
AG032554 / AG / NIA NIH HHS / United States
AG13616 / AG / NIA NIH HHS / United States

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