Mild Cognitive Impairment and Alzheimer Disease: Patterns of Altered Cerebral Blood Flow at MR Imaging

Abstract

Purpose To examine regional cerebral blood flow (rCBF) in incident mild cognitive impairment (MCI) and Alzheimer disease (AD) by using continuous arterial spin-labeling (CASL) magnetic resonance (MR) imaging. Materials and Methods This study was approved by the local institutional review board and was compliant with HIPAA regulations. Informed consent was obtained. rCBF was measured in 38 control subjects, 29 MCI patients, and 37 AD patients who were participating in a longitudinal epidemiologic study. Multisection CASL MR imaging with alternating single and double adiabatic inversion pulses and ramp-sampled echo-planar imaging were performed to acquire 19 contiguous axial sections. Voxel-level rCBF was compared among groups by using an analysis of variance design; clusters of voxels with significant group differences were identified. Multiple regression models controlled for age, sex, and presence of hypertension and related the mean rCBF in those clusters to the presence of MCI and AD. Results MCI and AD patients had decreased rCBF in the posterior cingulate gyrus (P =.01) with extension to the medial precuneus compared with that in control subjects. MCI patients had increased rCBF in the left hippocampus (P <.001), right amygdala (P =.007), and rostral head of the right caudate nucleus and ventral putamen and globus pallidus (P =.003) compared with that in control subjects. AD patients had decreased rCBF relative to that in control subjects and MCI patients in the left inferior parietal (P =.005), left lateral frontal (P <.001), left superior temporal (P =.001), and left orbitofrontal (P =.003) cortices. AD patients had increased rCBF in the right anterior cingulate gyrus (P =.02) compared with that in control subjects. Conclusion The transition from normal cognition to AD is associated with dynamic pathologic processes in the brain, and this is reflected by both decreases and increases in rCBF. Increases in rCBF suggest a cellular and vascular compensatory process associated with incipient AD.

Framingham Cardiovascular Risk Profile Correlates with Impaired Hippocampal and Cortical Vasoreactivity to Hypercapnia

“…We offer that preexisting vessel impairment (independent of vascular risk, but possibly related to AD) had to be present to potentiate the influence of vascular risk factors on vessel expandability. Opposite to earlier findings (Dai et al, 2009;Staffen et al, 2006;Hirao et al, 2005;Caroli et al, 2007), CBF was not different between NL and MCI. Global CBF was, however, related to the global cognitive abilities as assessed with MMSE.…”

Pathophysiology of Hypoperfusion of the Precuneus in Early Alzheimer's Disease

“…The present findings indicate that these changes are not simply late‐stage manifestations of AD but are demonstrable even in early AD (ie, in Braak stage III–IV disease) in the precuneus, a region that is amongst the first affected by hypoperfusion 2, 6, 7, 13, 28, 30, 53. Indeed, the MAG:PLP1 ratio, an indicator of the adequacy of ante‐mortem tissue oxygenation, was lower in early than late AD (Braak stage V–VI) when the reduction was less pronounced, possibly reflecting falling oxygen demand, for example, as a result of reduced synaptic activity.…”

“…Blood flow and glucose utilization decline in the precuneus at a very early stage of Alzheimer's disease (AD) 2, 6, 7, 13, 28, 30, 53. Reduction in cerebral blood flow precedes the development of dementia in AD 52 and occurs well before any behavioral or pathological abnormalities in animal models of the disease 24, 39.…”

Effect of Mild Cognitive Impairment and APOE Genotype on Resting Cerebral Blood Flow and its Association with Cognition

“…Increased CBF in the left medial frontal gyrus was only correlated with verbal memory for MCI e4 adults. Regional increases in CBF have been interpreted as indicating a cellular and vascular compensatory process in response to pathologic damage associated with incipient AD (Dai et al, 2009), whereas decreases in CBF are thought to reflect decreases in brain function. Neural activity results in increased blood flow (i.e., delivery of glucose and oxygen) and metabolism in the brain.…”