The effect of ApoE ε4 on longitudinal brain region-specific glucose metabolism in patients with mild cognitive impairment: a FDG-PET study

We investigate whether the apolipoprotein E ε4 allele exhibits brain region specific effects in longitudinal glucose uptake among patients with mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative

Manish D. Paranjpe; Xueqi Chen; Min Liu; Ishan Paranjpe; Jeffrey P. Leal; Rongfu Wang; Martin G. Pomper; Dean F. Wong; Tammie L.S. Benzinger; Yun Zhou


Scholarcy highlights

  • Alzheimer's disease is characterized by memory loss and cognitive decline
  • We tested the effect of apolipoprotein E ε4 allele on cognitive decline in our study cohort by assessing the significance of ApoE:time interaction term and found that ApoE ε4 carriers exhibit significantly greater declines in Mini-Mental State Exam, Functional Activities Questionnaire, Clinical Dementia Rating, Geriatric Depression Scale, and ADAS-cog11 and ADAS-cog13 compared to ApoE ε4 non-carriers over the study period
  • We found region of interest of the superior frontal cortex, amygdala, caudate, parietal cortex, posterior cingulate, lateral temporal and medial temporal and thalamic brain regions had significantly greater longitudinal decreases in FDG uptake in ApoE ε4 carriers compared to non-carriers for partial volume correction based standardized uptake value ratio
  • Among ApoE ε4 non-carriers, we found 4 significant clusters after cluster-level correction. a Cluster p value was corrected for Family-wise error rate using SPM12. b Coordinates are in Montreal Neurologic Institute space based on the output from SPM12. c MNI coordinates were mapped to the nearest gray matter brain region and Brodmann area using Talairach Client
  • We assessed the effect of the ApoE ε4 allele on glucose metabolism in mild cognitive impairment and elucidated a novel, regional pattern of glucose hypometabolism over up to 84-months longitudinal follow-up period
  • We found no significant difference in longitudinal decline in Neuropsychiatric Inventory Questionnaire score between carriers and non-carriers
  • The superior fontal, parietal, lateral temporal, medial temporal, caudate, thalamus, and post-cingulate, and amygdala regions show greater longitudinal decreases in FDG uptake in ApoE ε4 carriers compared to non-carriers in the context of MCI
  • Our work represents one of the longest FDG studies of mild cognitive impairment, and uncovers a novel apolipoprotein E ε4-associated metabolic dynamic pattern in patients with MCI

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