Neural deterioration and compensation in visual short-term memory among individuals with amnestic mild cognitive impairment

Abstract

Introduction: Visual short-term memory (VSTM) is a critical indicator of Alzheimer's disease (AD), but whether its neural substrates could adapt to early disease progression and contribute to cognitive resilience in amnestic mild cognitive impairment (aMCI) has been unclear.

Methods: Fifty-five aMCI patients and 68 normal controls (NC) performed a change-detection task and underwent multimodal neuroimaging scanning.

Results: Among the atrophic brain regions in aMCI, VSTM performance correlated with the volume of the right prefrontal cortex (PFC) but not the medial temporal lobe (MTL), and this correlation was mainly present in patients with greater MTL atrophy. Furthermore, VSTM was primarily correlated with frontal structural connectivity in aMCI but was correlated with more distributed frontal and MTL connectivity in NC.

Discussion: This study provided evidence on neural adaptation in the precursor stages of AD, highlighting the compensatory role of PFC as MTL deteriorated and suggesting potential targets in early intervention for cognitive preservation.

Highlights: Atrophic left medial temporal lobe (MTL) no longer correlated with visual short-term memory (VSTM) in amnestic mild cognitive impairment (aMCI). Atrophic right middle frontal area continued to correlate with VSTM in aMCI. Frontal brain-behavior correlation was mainly present in the aMCI subgroup with greater medial temporal lobe (MTL) atrophy. Reliance of VSTM on frontal connectivity increased in compensation for MTL dysfunction.

Keywords: Alzheimer's disease; amnestic mild cognitive impairment; cognitive resilience; medial temporal lobe; prefrontal compensation; prefrontal cortex; visual short‐term memory.

FIGURE 1

A, Stimuli and trial procedure of visual change detection task. B–D, Performance of change detection task. Error bar represents standard error. Age, sex, education, and collection site were used as covariates. *p < 0.05; **p < 0.005; ***p < 0.001. aMCI, amnestic mild cognitive impairment; NC, normal control; RT, reaction time.

FIGURE 2

A, Structural atrophy in aMCI group compared to NC group. Voxel‐wise threshold p < 0.005, cluster‐level threshold p < 0.05 with GRF correction, gray matter mask applied. B, Significant structural differences between NC and aMCI group. Error bar represents standard error. **p < 0.005; ***p < 0.001. C, Relationship between structural GMV of left MTL and performance of change detection task for each group. D, Relationship between structural GMV of right MFG and performance of change detection task for each group. Age, sex, education, TIV, and collecting site were used as covariates for the analysis above. aMCI, amnestic mild cognitive impairment; GRF, Gaussian random field; GMV, gray matter volume; HP, hippocampus; L, left; MFG, middle frontal gyrus; MTL, medial temporal lobe; NC, normal control; postCG, postcentral gyrus; R, right; TIV, total intracranial volume.

FIGURE 3

A, Right SFG/MFG (target) area showed significant between‐group difference in functional connectivity to left MTL (ROI seed). Voxel‐wise threshold p < 0.005, cluster‐wise threshold p < 0.05 with GRF correction, gray matter mask applied and age, sex, education, and collecting site as covariates. B, Significant between‐group difference in functional connectivity between left MTL and right SFG/MFG. Error bar represents standard error; ***p < 0.001. C, Display of the right frontal areas. Red, the right SFG/MFG in functional results; blue, the right MFG in structural results; green, overlap area. aMCI, amnestic mild cognitive impairment; GRF, Gaussian random field; MCI, mild cognitive impairment; L, left; MFG, middle frontal gyrus; MTL, medial temporal lobe; NC, normal control; R, right; ROI, region of interest; SFG, superior frontal gyrus.

FIGURE 4

Relationship between GMV of right MFG and VSTM performance influenced by the GMV of left MTL in the aMCI group. Age, sex, education, TIV and collecting site were used as covariates. aMCI, amnestic mild cognitive impairment; GMV, gray matter volume; GRF, Gaussian random field; L, left; LV, subgroup with larger volume of left MTL; MFG, middle frontal gyrus; MTL, medial temporal lobe; R, right; SV, subgroup with smaller volume of left MTL.

FIGURE 5

Structural connections with significant loadings (P_FDR  < 0.001) in canonical correlation with measures of WM performance (two‐item and four‐item response accuracies, capacity) for (A) the aMCI group and (B) the NC group, respectively. Line color represents loading correlation coefficient (sign corrected to indicate direction of correlation with WM variables, not the X variate). aHPC, anterior hippocampus; aMCI, amnestic mild cognitive impairment; AMG, amygdala; BSTS, banks of superior temporal sulcus; cACC, caudal anterior cingulate cortex; CER, cerebellum; cMFG: caudal middle frontal gyrus; ERC, entorhinal cortex; FDR, false discovery rate; FG, fusiform gyrus; FP, frontal pole; ICC, isthmus cingulate cortex; IN, insula; IPL, inferior parietal lobe; LG, lingual gyrus; lOFC, lateral orbitofrontal cortex; NC, normal control; parOB, pars orbitalis; parOP, pars opercularis; parTR, pars triangularis; pHPC, posterior hippocampus; posCen, postcentral gyrus; PRC, perirhinal cortex Brodmann area 35; preCen, precentral gyrus; preCU, precuneous; PUT, putamen; rMFG, rostral middle frontal gyrus; SFG, superior frontal gyrus; SPL, superior parietal lobe; TH, thalamus; TP, temporal pole; WM, white matter.