TY - JOUR
T1 - Functional brain network centrality is related to APOE genotype in cognitively normal elderly
AU - Wink, Alle Meije
AU - Tijms, Betty M.
AU - ten Kate, Mara
AU - Raspor, Eva
AU - de Munck, Jan C.
AU - Altena, Ellemarije
AU - Ecay-Torres, Mirian
AU - Clerigue, Montserrat
AU - Estanga, Ainara
AU - Garcia-Sebastian, Maite
AU - Izagirre, Andrea
AU - Martinez-Lage Alvarez, Pablo
AU - Villanua, Jorge
AU - Barkhof, Frederik
AU - Sanz-Arigita, Ernesto
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Introduction: Amyloid plaque deposition in the brain is an early pathological change in Alzheimer's disease (AD), causing disrupted synaptic connections. Brain network disruptions in AD have been demonstrated with eigenvector centrality (EC), a measure that identifies central regions within networks. Carrying an apolipoprotein (APOE)-ε4 allele is a genetic risk for AD, associated with increased amyloid deposition. We studied whether APOE-ε4 carriership is associated with EC disruptions in cognitively normal individuals. Methods: A total of 261 healthy middle-aged to older adults (mean age 56.6 years) were divided into high-risk (APOE-ε4 carriers) and low-risk (noncarriers) groups. EC was computed from resting-state functional MRI data. Clusters of between-group differences were assessed with a permutation-based method. Correlations between cluster mean EC with brain volume, CSF biomarkers, and psychological test scores were assessed. Results: Decreased EC in the visual cortex was associated with APOE-ε4 carriership, a genetic risk factor for AD. EC differences were correlated with age, CSF amyloid levels, and scores on the trail-making and 15-object recognition tests. Conclusion: Our findings suggest that the APOE-ε4 genotype affects brain connectivity in regions previously found to be abnormal in AD as a sign of very early disease-related pathology. These differences were too subtle in healthy elderly to use EC for single-subject prediction of APOE genotype.
AB - Introduction: Amyloid plaque deposition in the brain is an early pathological change in Alzheimer's disease (AD), causing disrupted synaptic connections. Brain network disruptions in AD have been demonstrated with eigenvector centrality (EC), a measure that identifies central regions within networks. Carrying an apolipoprotein (APOE)-ε4 allele is a genetic risk for AD, associated with increased amyloid deposition. We studied whether APOE-ε4 carriership is associated with EC disruptions in cognitively normal individuals. Methods: A total of 261 healthy middle-aged to older adults (mean age 56.6 years) were divided into high-risk (APOE-ε4 carriers) and low-risk (noncarriers) groups. EC was computed from resting-state functional MRI data. Clusters of between-group differences were assessed with a permutation-based method. Correlations between cluster mean EC with brain volume, CSF biomarkers, and psychological test scores were assessed. Results: Decreased EC in the visual cortex was associated with APOE-ε4 carriership, a genetic risk factor for AD. EC differences were correlated with age, CSF amyloid levels, and scores on the trail-making and 15-object recognition tests. Conclusion: Our findings suggest that the APOE-ε4 genotype affects brain connectivity in regions previously found to be abnormal in AD as a sign of very early disease-related pathology. These differences were too subtle in healthy elderly to use EC for single-subject prediction of APOE genotype.
KW - APOE-ε4
KW - Alzheimer's disease
KW - amyloid
KW - eigenvector centrality
KW - functional MRI
KW - visual cortex
UR - http://www.scopus.com/inward/record.url?scp=85052504819&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/brb3.1080
DO - https://doi.org/10.1002/brb3.1080
M3 - Article
C2 - 30136422
SN - 2162-3279
VL - 8
JO - Brain and behavior
JF - Brain and behavior
IS - 9
M1 - e01080
ER -