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[IC‐P‐056]: ADORA2A POLYMORPHISM IS ASSOCIATED WITH CEREBRAL BLOOD FLOW IN MILD COGNITIVE IMPAIRMENT (MCI) AND ALZHEIMER'S DISEASE
Author(s) -
Horgusluoglu Emrin,
Risacher Shan L.,
Saykin Andrew J.,
Nho Kwangsik
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.2329
Subject(s) - cerebral blood flow , adenosine a2a receptor , medicine , minor allele frequency , neuroimaging , neuroscience , statistical parametric mapping , cardiology , cognitive decline , adenosine , temporal lobe , endocrinology , pathology , psychology , dementia , adenosine receptor , allele , receptor , magnetic resonance imaging , biology , allele frequency , disease , epilepsy , radiology , biochemistry , gene , agonist
and distribution of gray matter atrophy of ε2 carriers with MCI or dementia -due-to-AD.Methods:38 ε2 carriers (all ε2/ε3) with a clinical diagnosis ofMCI or dementia -due-to-AD based on positive amyloid PET and/or CSF amyloid-beta1-42 were included. This group was matched for age, sex and education with an amyloid-negative cognitively normal ε3/ε3 (NC) group, and groups of amyloid-positive ε3/ε3, ε3/ε4, and ε4/ε4 AD patients (Table 1). Neuropsychological test scores were converted into Z-scores using the mean and standard deviation of the NC group and then categorized into 4 cognitive domains (i.e. memory, attention, executive functioning and language). ANCOVA analyses adjusted for age, sex, education and disease-stage (MCI/ dementia) were used to compare cognition between AD groups. Voxel-based morphometry was conducted in statistical parametric mapping 12 to assess voxelwise differences in gray matter atrophy between AD groups and controls. The models included age, sex, scanner-type and total intracranial volume as covariates. Results: ε2 carriers had more impaired language function compared to all other AD groups (F(3)1⁄46.29, p<.01; Figure 1), while memory was relatively preserved in ε2 carriers compared to ε4/ε4 carriers (F(3)1⁄42.67, p1⁄4.05). Voxelwise contrasts against controls revealed relative sparing of the medial temporal lobe in ε2 compared to ε4 carriers (p<.05, family-wise error corrected; Figure 2). Similar analyses using a less stringent threshold (p<.001, uncorrected; Figure 3) revealed that ε2 carriers displayed i) an atrophy pattern that was mostly restricted to temporoparietal regions compared to wider neocortical involvement in other groups, and ii) left>right asymmetry. Conclusions: The observed atrophy pattern in ε2 carriers (i.e. left>right asymmetry and relatively sparedmedial temporal lobes)matches their neuropsychological profilewith prominent language deficits and relatively preserved memory performance. These results help to elucidate differences in regional vulnerability across APOE genotypes and better understand clinical heterogeneity in AD.