TY - JOUR
T1 - Gray Matter Network Disruptions and Regional Amyloid Beta in Cognitively Normal Adults
AU - ten Kate, Mara
AU - Visser, Pieter Jelle
AU - Bakardjian, Hovagim
AU - Barkhof, Frederik
AU - Sikkes, Sietske A. M.
AU - van der Flier, Wiesje M.
AU - Scheltens, Philip
AU - Hampel, Harald
AU - Habert, Marie-Odile
AU - Dubois, Bruno
AU - Tijms, Betty M.
AU - Insight-PreAD Study Grp
PY - 2018/3/15
Y1 - 2018/3/15
N2 - The accumulation of amyloid plaques is one of the earliest pathological changes in Alzheimer's disease (AD) and may occur 20 years before the onset of symptoms. Examining associations between amyloid pathology and other early brain changes is critical for understanding the pathophysiological underpinnings of AD. Alterations in gray matter networks might already start at early preclinical stages of AD. In this study, we examined the regional relationship between amyloid aggregation measured with positron emission tomography (PET) and gray matter network measures in elderly subjects with subjective memory complaints. Single-subject gray matter networks were extracted from T1-weigthed structural MRI in cognitively normal subjects (n = 318, mean age 76.1 +/- 3.5, 64% female, 28% amyloid positive). Degree, clustering, path length and small world properties were computed. Global and regional amyloid load was determined using [F-18]-Florbetapir PET. Associations between standardized uptake value ratio (SUVr) values and network measures were examined using linear regression models. We found that higher global SUVr was associated with lower clustering (beta = -0.12, p < 0.05), and small world values (beta = -0.16, p < 0.01). Associations were most prominent in orbito-and dorsolateral frontal and parieto-occipital regions. Local SUVr values showed less anatomical variability and did not convey additional information beyond global amyloid burden. In conclusion, we found that in cognitively normal elderly subjects, increased global amyloid pathology is associated with alterations in gray matter networks that are indicative of incipient network breakdown towards AD dementia.
AB - The accumulation of amyloid plaques is one of the earliest pathological changes in Alzheimer's disease (AD) and may occur 20 years before the onset of symptoms. Examining associations between amyloid pathology and other early brain changes is critical for understanding the pathophysiological underpinnings of AD. Alterations in gray matter networks might already start at early preclinical stages of AD. In this study, we examined the regional relationship between amyloid aggregation measured with positron emission tomography (PET) and gray matter network measures in elderly subjects with subjective memory complaints. Single-subject gray matter networks were extracted from T1-weigthed structural MRI in cognitively normal subjects (n = 318, mean age 76.1 +/- 3.5, 64% female, 28% amyloid positive). Degree, clustering, path length and small world properties were computed. Global and regional amyloid load was determined using [F-18]-Florbetapir PET. Associations between standardized uptake value ratio (SUVr) values and network measures were examined using linear regression models. We found that higher global SUVr was associated with lower clustering (beta = -0.12, p < 0.05), and small world values (beta = -0.16, p < 0.01). Associations were most prominent in orbito-and dorsolateral frontal and parieto-occipital regions. Local SUVr values showed less anatomical variability and did not convey additional information beyond global amyloid burden. In conclusion, we found that in cognitively normal elderly subjects, increased global amyloid pathology is associated with alterations in gray matter networks that are indicative of incipient network breakdown towards AD dementia.
KW - amyloid beta
KW - PET
KW - gray matter network
KW - graph theory
KW - MRI
KW - subjective memory complaints
KW - Alzheimer's disease
KW - POSITRON-EMISSION-TOMOGRAPHY
KW - PRECLINICAL ALZHEIMERS-DISEASE
KW - HUMAN CORTICAL NETWORKS
KW - BRAIN NETWORKS
KW - STRUCTURAL COVARIANCE
KW - PROSPECTIVE COHORT
KW - SPATIAL-PATTERNS
KW - CEREBRAL-CORTEX
KW - PLAQUE BURDEN
KW - APOE GENOTYPE
U2 - 10.3389/fnagi.2018.00067
DO - 10.3389/fnagi.2018.00067
M3 - Article
C2 - 29599717
SN - 1663-4365
VL - 10
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
M1 - 67
ER -