Resting-state BOLD networks versus task-associated functional MRI for distinguishing Alzheimer's disease risk groups

Abstract

To assess the ability of resting state functional magnetic resonance imaging to distinguish known risk factors for AD, we evaluated 17 cognitively normal individuals with a family history of AD and at least one copy of the apolipoprotein e4 allele compared to 12 individuals who were not carriers of the APOE4 gene and did not have a family history of AD. Blood oxygen level dependent fMRI was performed evaluating encoding-associated signal and resting state default mode network signal differences between the two risk groups. Neurocognitive testing revealed that the high risk group performed worse on category fluency testing, but the groups were equivalent on all other cognitive measures. During encoding of novel face-name pairs, there were no regions of encoding-associated BOLD activations that were different in the high risk group. Encoding-associated deactivations were greater in magnitude in the low risk group in the medial and right lateral parietal cortex, similar to findings in AD studies. The resting state DMN analysis demonstrated nine regions in the prefrontal, orbital frontal, temporal and parietal lobes that distinguished the two risk groups. Resting state DMN analysis could distinguish risk groups with an effect size of 3.35, compared to an effect size of 1.39 using encoding-associated fMRI techniques. Imaging of the resting state avoids performance related variability seen in activation fMRI, is less complicated to acquire and standardize, does not require radio-isotopes, and may be more effective at identifying functional pathology associated with AD risk compared to non-resting fMRI techniques.

Functional brain network centrality is related to APOE genotype in cognitively normal elderly

“…Overall, the most frequently reported changes are weakened DMN connectivity in middle‐aged and older subjects (Goveas et al., 2013; Machulda et al., 2011; Reiman et al., 1996; Sheline et al., 2010; Wang et al., 2012) and, less frequently, increased DMN connectivity in young adults (Filippini et al., 2009; Fleisher et al., 2009). Our results demonstrate early visual effects in a population study with realistic proportions of carriers and noncarriers, which shows the applicability of functional measures in a community setting.…”

Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

“…the interplay between a set cortical areas and the hippocampal memory system [228], the activity of which is thought to be reduced during memory intensive tasks to favor encoding and to be increased during retrieval [229]. Several studies have found dysfunctional modulation of encoding-related network activity in AD [227,[230][231][232][233] or abnormal default mode pattern activity in AD and MCI patients using resting-state fMRI [234][235][236][237][238]. Interestingly, these results in MCI subjects have been correlated with a higher risk of progressing to AD-related dementia [239].…”

Recent developments of functional magnetic resonance imaging research for drug development in Alzheimer's disease

“…In addition, a recent study found that the DMN was more sensitive in discriminating between carrier and non-carriers of the APOE e4 allele, a risk factor for AD, than the activation pattern during a memory encoding task (Fleisher et al 2009). Given that the DMN includes the medial temporal lobes and the posterior cingulate, two areas key in memory and disrupted in AD patients, it offers the possibility to investigate medial temporal lobe function in AD patients without the use of a cognitive paradigm.…”