Devous Sr MD, Kennedy KM, Rodrigue KM, Hebrank AC, Park DC.
Precuneus beta-amyloid burden correlates with altered cortical network function in a lifespan sample of healthy adults.
Human Amyloid Imaging 2011 Meeting Abstracts. 2011 Jan 15;
There is evidence that amyloid burden (As) alters functional connectivity (FC) in subjects with Alzheimer's Disease
and Mild Cognitive Impairment and in elderly controls. We extended these studies by examining the relationship
between As and FC in a large lifespan sample of healthy controls (Dallas Lifespan Brain Study). BOLD at rest
(fcMRI) was measured within a continuous age sample of healthy adults (N = 137; 30-89 years old), and FC was
determined as z-score-normalized temporal correlation coefficients based on seeds placed in posterior cingulate
to represent the Default Mode Network (DMN) and anterior cingulate to represent the Salience Network (SN).
Participants also underwent PET scanning using 18Florbetapir to measure As, expressed as standardized uptake
value ratios to cerebellum (SUVR), using a precuneus ROI for these analyses. Relationships between As and
fcMRI in DMN and SN were examined both as continuous variables and by contrasting subjects with high As
against an age- and gender-matched group of low As subjects (N = 25 each). Precuneus As across the lifespan
was associated with decreased connectivity to the DMN in right precuneus and left orbital frontal cortex and with
increased connectivity in left medial temporal lobe, superior middle cingulate, and lateral peri-sylvian temporal
lobe. In contrast, reduction in connectivity to the SN (in the resting state) was minimally affected by precuneus As,
while substantially increased connectivity was seen in bilateral insula, inferior striatum (near nucleus accumbens),
hippocampus and dorsolateral prefrontal cortex. Between-group comparisons (high vs. low As) revealed significant
decreases in frontal connectivity associated with elevated As in the DMN, while increased lateral temporal and
insular connectivity was seen in the SN . a finding mimicking data in Alzheimer's Disease. Thus increasing amyloid
burden exerts negative effects on functional connectivity such that the DMN is less connected with increasing As
and SN connectivity is inappropriately increased.
Supported in part by NIH grants 5R37AG-006265-25, 3R37AG-006265-25S1, and Alzheimer's Association grant
IIRG-09-135087. Radiotracer was generously provided to the study by Avid Radiopharmaceuticals.