Insula and Inferior Frontal Gyrus’ Activities Protect Memory Performance Against Alzheimer’s Disease Pathology in Old Age

Abstract

Apolipoprotein E (APOE) ε4 carriers and patients with amnestic mild cognitive impairment (MCI) have high risk of developing Alzheimer's disease (AD). The Scaffolding Theory of Aging and Cognition proposes that recruitment of additional frontal brain regions can protect cognition against aging. This thesis has yet to be fully tested in older adults at high risk for AD. In the present study, 75 older participants (mean age: 74 years) were included. Applying a voxel-wise approach, fractional amplitude of low-frequency fluctuations (fALFF) in resting-state functional neuroimaging data were analyzed as a function of APOEε4 status (carrier vs. noncarrier) and clinical status (healthy control [HC] vs. MCI) using a 2×2 analysis of covariance (ANCOVA). Measures of cognition and cerebrospinal fluid levels of amyloid-beta were also obtained. Three frontal regions were identified with significant interaction effects using ANCOVA (corrected p < .01): left-insula, left-inferior frontal gyrus (IFG), and right-precentral gyrus. The HC/APOEε4 carrier group had significantly higher fALFF in all three regions than other groups. In the entire sample, for two regions (left insula and left IFG), a significant positive relationship between β-amyloid and memory was only observed among individuals with low fALFF. Our results suggest higher activity in frontal regions may explain being cognitively normal among a subgroup of APOEε4 carriers and protect against the negative impact of AD-associated pathology on memory. This is an observation with potential implications for AD therapeutics.

Different Cortical Gyrification Patterns in Alzheimer's Disease and Impact on Memory Performance

“…44 An overactivation of the left insular and left inferior frontal cortices was also found to protect memory function in healthy participants at high risk of AD during resting state. 49 Additionally, the strength of the connections between the insula and several frontal regions has been associated with better episodic memory in amnestic MCI patients. 50 In light of our results and previous literature, the insular cortex appears to be fundamentally and specifically involved in the memory function of demented patients, either by participating directly in the memory process or by facilitating the engagement of frontal regions.…”

Distinct Spontaneous Brain Activity Patterns in Different Biologically-Defined Alzheimer’s Disease Cognitive Stage: A Preliminary Study

“…Under the impact of amyloid and tau pathology, we interpreted the hyperactivity in the IFG as compensational effects so that the individuals could maintain normal cognitive performance for a period. Recently, Lin et al (2017) have found that higher activity and stronger functional connectivity in the IFG and insula may protect memory performance against AD-associated pathology. Moreover, the higher BOLD signal in the IFG during the encoding process also has been found in participants classified into a successful group according to performance in the memory task (Pudas et al, 2013).…”

Pro‐neurocognitive and anti‐sarcopenic benefits of one‐year metformin therapy in ovariectomized aged mice

“…Aging affects the various aspects of cognitive function and the risk of cognitive decline increases with age. It has been documented that cognitive functions such as memory are influenced during aging, which may be related to neuron loss in certain regions of the brain . Long‐term loss of the ovary function significantly increases the risk of dementia and mortality due to neurological disorders .…”