Relationships between hippocampal atrophy, white matter disruption, and gray matter hypometabolism in Alzheimer's disease.
In early Alzheimer's disease (AD), the hippocampal region is the area most severely affected by cellular and structural alterations, yet glucose hypometabolism predominates in the posterior association cortex and posterior cingulate gyrus. One prevalent hypothesis to account for this discrepancy is that posterior cingulate hypometabolism results from disconnection from the hippocampus through disruption of the cingulum bundle. However, only partial and indirect evidence currently supports this hypothesis. Thus, using structural magnetic resonance imaging and 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography in 18 patients with early AD, we assessed the relationships between hippocampal atrophy, white matter integrity, and gray matter metabolism by means of a whole-brain voxel-based correlative approach. We found that hippocampal atrophy is specifically related to cingulum bundle disruption, which is in turn highly correlated to hypometabolism of the posterior cingulate cortex but also of the middle cingulate gyrus, thalamus, mammillary bodies, parahippocampal gyrus, and hippocampus (all part of Papez's circuit), as well as the right temporoparietal associative cortex. These results provide the first direct evidence supporting the disconnection hypothesis as a major factor contributing to the early posterior hypometabolism in AD. Disruption of the cingulum bundle also appears to relate to hypometabolism in a large connected network over and above the posterior cingulate cortex, encompassing the whole memory circuit of Papez (consistent with the key location of this white matter tract within this loop) and also, but indirectly, the right posterior association cortex.
Institut National de la Santé et de la Recherche Médicale-Ecole Pratique des Hautes Etudes-Université de Caen/Basse-Normandie, Unité U923, Groupement d'Intérêt Public Cyceron, Centre Hospitalier Universitaire Côte de Nacre, 14074 Caen, France.
Nicolas
N
Villain
Béatrice
B
Desgranges
Fausto
F
Viader
Vincent
V
de la Sayette
Florence
F
Mézenge
Brigitte
B
Landeau
Jean-Claude
JC
Baron
Francis
F
Eustache
Gaël
G
Chételat
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology*; D001284:Atrophy; D001931:Brain Mapping; D016022:Case-Control Studies; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000000981:diagnostic imaging / Q000473:pathology*; D009474:Neurons / Q000000981:diagnostic imaging / Q000473:pathology*; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods; D013223:Statistics as Topic
D019788:Fluorodeoxyglucose F18