Local Functional MR Change Pattern and Its Association With Cognitive Function in Objectively-Defined Subtle Cognitive Decline

Abstract

Introduction: To identify individuals with preclinical cognitive impairment, researchers proposed the concept of objectively-defined subtle cognitive decline (Obj-SCD). However, it is not clear whether Obj-SCD has characteristic brain function changes. In this study, we aimed at exploring the changing pattern of brain function activity in Obj-SCD individuals and the similarities and differences with mild cognitive impairments (MCI). Method: 37 healthy control individuals, 25 Obj-SCD individuals (with the impairment in memory and language domain), and 28 aMCI individuals were included. Resting-state fMRI and neuropsychological tests were performed. fALFF was used to reflect the local functional activity and compared between groups. Finally, we analyzed the correlation between the fALFF values of significantly changed regions and neuropsychological performance. Results: We found similar functional activity enhancements in some local brain regions in the Obj-SCD and aMCI groups, including the left orbital part of the inferior frontal gyrus and the left median cingulate and paracingulate gyri. However, some changes in local functional activities of the Obj-SCD group showed different patterns from the aMCI group. Compared with healthy control (HC), the Obj-SCD group showed increased local functional activity in the right middle occipital gyrus, decreased local functional activity in the left precuneus and the left inferior temporal gyrus. In the Obj-SCD group, in normal band, the fALFF value of the right middle occipital gyrus was significantly negatively correlated with Mini-Mental State Examination (MMSE) score (r = -0.450, p = 0.024) and Animal Verbal Fluency Test (AFT) score (r = -0.402, p = 0.046); the left inferior temporal gyrus was significantly positively correlated with MMSE score (r = 0.588, p = 0.002). In slow-4 band, the fALFF value of the left precuneus was significantly positively correlated with MMSE score (r = 0.468, p = 0.018) and AFT score (r = 0.600, p = 0.002). In the aMCI group, the fALFF value of the left orbital part of the inferior frontal gyrus was significantly positively correlated with Auditory Verbal Learning Test (AVLT) long delay cued recall score (r = 0.506, p = 0.006). Conclusion: The Obj-SCD group showed a unique changing pattern; the functional changes of different brain regions have a close but different correlation with cognitive impairment, indicating that there may be a complex pathological basis inside. This suggests that Obj-SCD may be a separate stage of cognitive decline before aMCI and is helpful to the study of preclinical cognitive decline.

Keywords: cognitive function; function activity; mild cognitive impairment; objectively-defined subtle cognitive decline; resting-state functional MRI.

Figure 1

Local functional change pattern of Obj-SCD group. The Obj-SCD group compared with the HC group. (A) In the normal band, fALFF increased in the left orbital part of inferior frontal gyrus, the right middle occipital gyrus, cerebellar vermis; decreased fALFF in the left inferior temporal gyrus (Two-tailed t-test; FDR p < 0.017, k > 10 voxels). (B) In the slow-4 band, fALFF increased in the left median cingulate and paracingulate gyri; decreased in the left inferior temporal gyrus and the left precuneus (Two-tailed t-test; FDR p < 0.017, k > 10 voxels). (C) In the slow-5 band, fALFF increased in the right middle occipital gyrus, caudate nucleus, and cerebellar vermis (Two-tailed t-test; FDR p < 0.017, k > 10 voxels). The numbers in brackets are voxels of significant clusters. Labels of significant clusters are defined with the AAL (Anatomical Automatic Labeling) atlas. Abbreviations: Obj-SCD, objectively-defined subtle cognitive decline; fALFF, low-frequency fluctuation amplitude (ALFF); HC, healthy control; FDR, false discovery rate.

Figure 2

Local functional change pattern of aMCI group. (A) In the normal band, compared with the HC group, the aMCI group showed increased fALFF in the left orbital part of the inferior frontal gyrus, bilateral median cingulate, and paracingulate gyri (Two-tailed t-test; FDR p < 0.001, k > 10 voxels). (B) In the slow-5 band, compared with the HC group, the aMCI group showed increased fALFF in the right median cingulate and paracingulate gyri (Two-tailed t-test; FDR p < 0.001, k > 10 voxels). (C) In the normal band, compared with the Obj-SCD group, the aMCI group showed decreased fALFF in the right middle occipital gyrus (Two-tailed t-test; FDR p < 0.017, k > 10 voxels). The numbers in brackets are voxels of significant clusters. Labels of significant clusters are defined with the AAL (Anatomical Automatic Labeling) atlas. Abbreviation: aMCI, amnestic MCI.

Figure 3

Correlation between local functional activity and neuropsychological performance. (A) In the Obj-SCD group, in the normal band, the fALFF value of the right middle occipital gyrus was significantly negatively correlated with the MMSE score and AFT score; the left inferior temporal gyrus was significantly positively correlated with the MMSE score. In the slow-4 band, the fALFF value of the left precuneus was significantly positively correlated with the MMSE and AFT scores. (B) In the aMCI group, the fALFF value of the left orbital part of the inferior frontal gyrus was significantly positively correlated with AVLT 6th recall score. *p < 0.05. Abbreviations: AFT, Animal Verbal Fluency Test; AVLT, Auditory Verbal Learning Test; MMSE, Mini-Mental State Examination.