Aberrant default mode network in subjects with amnestic mild cognitive impairment using resting-state functional MRI

Abstract

Amnestic mild cognitive impairment (aMCI) is a syndrome associated with faster memory decline than normal aging, and frequently represents the prodromal phase of Alzheimer’s disease. When a person is not actively engaged in a goal-directed task, spontaneous functional magnetic resonance imaging (fMRI) signals can reveal functionally connected brain networks, including the so-called default mode network (DMN). To date, only a few studies have investigated DMN functions in aMCI populations. In this study, group independent component analysis was conducted for resting-state fMRI data, with slices acquired perpendicular to the long axis of the hippocampus, from eight subjects with aMCI and eight normal control subjects. Subjects with aMCI showed increased DMN activity in middle cingulate cortex, medial prefrontal cortex, and left inferior parietal cortex compared to the normal control group. Decreased DMN activity for the aMCI group compared to the normal control group was noted in lateral prefrontal cortex, left medial temporal lobe (MTL), left medial temporal gyrus, posterior cingulate cortex/retrosplenial cortex/precuneus, and right angular gyrus. Although MTL volume difference between the two groups was not statistical significant, decreased activity in left MTL was observed for the aMCI group. Positive correlations between DMN activity and memory scores were noted for left lateral prefrontal cortex, left medial temporal gyrus, and right angular gyrus. These findings support the premise that alterations of the DMN occur in aMCI and may indicate deficiencies in functional, intrinsic brain architecture, that correlate with memory function, even before significant medial temporal lobe atrophy is detectable by structural MRI.

Attenuated anticorrelation between the default and dorsal attention networks with aging: evidence from task and rest

“…Consistent with the critical role of the MTL in episodic memory (Squire et al, 2004) and the marked deficits in episodic memory in age-related dementia, several studies have demonstrated reduced RSFC of the MTL in particular with other default network regions in individuals with mild cognitive impairment (Das et al, 2013; Das et al, 2015; Jin, Pelak, & Cordes, 2012), and Alzheimer’s disease (for review see Hafkemeijer et al, 2012; Mevel et al, 2011), including patients in prodromal stages (Sperling et al, 2010; Wang et al, 2006). Episodic memory also shows declines in typical healthy aging (Grady, 2012) and there is evidence for MTL-cortical reductions in FC at rest with advancing age (Salami, Pudas & Nyberg, 2014).…”

Resting-state functional magnetic resonance imaging in patients with leukoaraiosis-associated subcortical vascular cognitive impairment: a cross-sectional study

“…22−24 A study combining rs-fMRI and cognitive tasks found that the activity decreased in the left medial temporal lobe, left medial temporal gyrus, posterior cingulate cortex/cingulate, lower precuneus and the right angular convolution apart from the lateral prefrontal cortex, and memory impairment was positively correlated with the activity of the left lateral prefrontal lobe and the right angular convolution (Table 4). 15 those of the control group, including the bilateral medial frontal gyrus (a), the bilateral medial temporal gyrus (b), the bilateral superior parietal lobe (c), the bilateral angular gyrus (d), the bilateral occipital lobes (e), and the posterior cingulate cortex/precuneus (f).…”

“…subcortical vascular cognitive impairment (SVCI) vs. amnestic mild cognitive impairment (aMCI)] indicated DMN as a potential marker for differential diagnosis. 15,16 Current medical workup for mild cognitive impairment includes medical history inquiry, independent function and daily activities assessment, input from relatives and caregivers, mental status assessment, in-office neurological examination, mood evaluation and laboratory tests, which largely relies on a physician's experience and judgment. Though the role of the DMN in human brain remains controversial, based on the studies mentioned above, it seems that the rs-fMRI signal changes could serve as a relatively objective marker for detecting significant functional alteration in patients at the early stage of dementia, such as SVCI and aMCI.…”

Synaptic function as a preclinical and experimental medicine readout for disease-modifying therapy in Alzheimer's Disease

“…Synaptic dysfunction results in abnormal plasticity in different brain regions leading to disruption in the organization of functional connectivity within [10,11] and between different brain regions [12][13][14][15]. Loss of functional connectivity in the brain [10,16] results in cognitive decline even at early stages of the disease like amnestic MCI [17,18] as well as in clinically normal subjects with high amyloid burden [19]. Electron microscopic analysis of post-mortem tissues or biopsied/autopsied cortical tissues revealed a significant correlation between reduction in synaptic density (15-35%) and a decline in episodic memory as reflected by MMSE score [20,21], as the disease progress from mild to moderate stages [22][23][24] (2-4 years after disease onset).…”