Functional Magnetic Resonance Imaging of Compensatory Neural Recruitment in Aging and Risk for Alzheimer’s Disease: Review and Recommendations

Abstract

There has been a recent proliferation of functional magnetic resonance imaging (fMRI) studies that interpret between-group or within-group differences in brain response patterns as evidence for compensatory neural recruitment. However, it is currently a challenge to determine whether these observed differences are truly attributable to compensatory neural recruitment or whether they are indicative of some other cognitive or physiological process. Therefore, the need for a standardized set of criteria for interpreting whether differences in brain response patterns are compensatory in nature is great. Focusing on studies of aging and potentially prodromal Alzheimer’s disease conditions (genetic risk, mild cognitive impairment), we critically review the functional neuroimaging literature purporting evidence for compensatory neural recruitment. Finally, we end with a comprehensive model set of criteria for ascertaining the degree to which a ‘compensatory’ interpretation may be supported. This proposed model addresses significant brain region, activation pattern, and behavioral performance considerations, and is therefore termed the Region-Activation-Performance model (RAP model).

Resting-State Functional Connectivity Changes Associated with Visuospatial Cognitive Deficits in Patients with Mild Alzheimer Disease

“…2b) [4]. Hypoconnectivity within DMN is possibly due to early amyloid deposition in regions with high metabolism (posterior cingulate-precuneus complex within the DMN) [13,14]. Reduced rsFC within DMN is observed in patients with presymptomatic AD (mild cognitive impairment) and cognitively normal elders with amyloid deposition [15,16,17,18].…”

“…Reduced rsFC within DMN is observed in patients with presymptomatic AD (mild cognitive impairment) and cognitively normal elders with amyloid deposition [15,16,17,18]. As rsFC of DMN is correlated with cognitive functions, DMN hypoconnectivity may reflect the core pathophysiology underlying verbal memory deficits in AD [15,16,18], while hyperconnectivity within the EN is attributed to compensatory mechanisms secondary to primary hypoconnectivity [13,14]. …”

Functional Magnetic Resonance Imaging in Aging and Dementia: Detection of Age-Related Cognitive Changes and Prediction of Cognitive Decline

“…One group (Bondi et al 2005;Han et al 2007Han et al , 2008 has proposed that the increased activation observed in asymptomatic carriers of the APOE e4 allele represents compensatory recruitment. They propose that the compensatory mechanism includes recruitment of additional brain regions and different patterns of activation in order to maintain or improve cognitive performance.…”

“…They propose that the compensatory mechanism includes recruitment of additional brain regions and different patterns of activation in order to maintain or improve cognitive performance. This RegionActivation-Performance model (Han et al 2008) infers that the function of the increased signal is to combat cognitive impairment in the presence of declining neural resources, and may be indicative of an increased risk for subsequent cognitive decline. Perhaps the early, more intensive, and possibly less efficient utilization of these neural structures by APOE e4 carriers may make them more susceptible to later degeneration and AD neuropathology.…”

“…The previously described study (Woodard et al 2010) observed that greater BOLD activation at baseline during a semantic memory task was protective against subsequent decline. However, several studies (Bondi et al 2005;Filippini et al 2009;Han et al 2008;Trivedi et al 2008;Seidenberg et al 2009a). Semantic memory activation have found that possession of the APOE e4 allele, a major risk factor for cognitive decline, is also associated with greater activation prior to the onset of cognitive impairment.…”