Lower Brain 18F-Fluorodeoxyglucose Uptake But Normal 11C-Acetoacetate Metabolism in Mild Alzheimer's Disease Dementia

被引:147
作者
Castellano, Christian-Alexandre [1 ,2 ]
Nugent, Scott [1 ,2 ]
Paquet, Nancy [3 ]
Tremblayd, Sebastien [4 ]
Bocti, Christian [1 ,3 ]
Lacombe, Guy [1 ,5 ]
Imbeault, Helene [1 ]
Turcotte, Eric [3 ,4 ]
Fulop, Tamas [1 ,5 ]
Cunnane, Stephen C. [1 ,5 ]
机构
[1] Geriatr Inst, Hlth & Social Sci Ctr, Res Ctr Aging, Sherbrooke, PQ, Canada
[2] Univ Sherbrooke, Dept Physiol & Biophys, Sherbrooke, PQ J1K 2R1, Canada
[3] Univ Sherbrooke, Dept Med Nucl & Radiobiol, Sherbrooke, PQ J1K 2R1, Canada
[4] Univ Sherbrooke, Sherbrooke Mol Imaging Ctr, Sherbrooke, PQ J1K 2R1, Canada
[5] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
Acetoacetate; Alzheimer's disease; beta-hydroxybutyrate; cerebral metabolic rate; energy metabolism; glucose; ketones; POSITRON-EMISSION-TOMOGRAPHY; DIMINISHED GLUCOSE-TRANSPORT; KETONE-BODIES; ENERGY-METABOLISM; LOW-CARBOHYDRATE; FUEL METABOLISM; FAMILY-HISTORY; PET; ATROPHY; DIET;
D O I
10.3233/JAD-141074
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: The cerebral metabolic rate of glucose (CMRg) is lower in specific brain regions in Alzheimer's disease (AD). The ketones, acetoacetate and beta-hydroxybutyrate, are the brain's main alternative energy substrates to glucose. Objective: To gain insight into brain fuel metabolism in mild AD dementia by determining whether the regional CMR and the rate constant of acetoacetate (CMRa and Ka, respectively) reflect the same metabolic deficit reported for cerebral glucose uptake (CMRg and Kg). Methods: Mild AD dementia (Mild AD; n = 10, age 76 y) patients were compared with gender-and age-matched cognitively normal older adults (Controls; n = 29, age 75 y) using a PET/MRI protocol and analyzed with bothROI- and voxel-based methods. Results: ROI-based analysis showed 13% lower global CMRg in the gray matter of mild AD dementia versus Controls (34.2 +/- 5.0 versus 38.3 +/- 4.7 mu mol/100 g/min, respectively; p = 0.015), with CMRg and Kg in the parietal cortex, posterior cingulate, and thalamus being the most affected (p <= 0.022). Neither global nor regional CMRa or Ka differed between the two groups (all p >= 0.188). Voxel-based analysis showed a similar metabolic pattern to ROI-based analysis with seven clusters of significantly lower CMRg in the mild AD dementia group (uncorrected p <= 0.005) but with no difference in CMRa. Conclusion: Regional brain energy substrate hypometabolism in mild AD dementia may be specific to impaired glucose uptake and/or utilization. This suggests a potential avenue for compensating brain energy deficit in AD dementia with ketones.
引用
收藏
页码:1343 / 1353
页数:11
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