Yonsei Med J.  2019 Oct;60(10):935-943. 10.3349/ymj.2019.60.10.935.

Distinct Neural Correlates of Executive Function by Amyloid Positivity and Associations with Clinical Progression in Mild Cognitive Impairment

• Yoon HJ
• Kim SG
• Kim SH
• Choo IH
• Park SH
• Seo EH
• For the Alzheimer's Disease Neuroimaging Initiative

• KMID: 2459146
• DOI: http://doi.org/10.3349/ymj.2019.60.10.935

Abstract

PURPOSE
This study aimed to identify the neural basis of executive function (EF) in amnestic mild cognitive impairment (aMCI) according to beta-amyloid (Aβ) positivity. Furthermore, we explored if the identified brain areas could serve as predictors for clinical progression.
MATERIALS AND METHODS
We included individuals with aMCI using data from [¹â¸F]-florbetapir-positron emission tomography (PET), fluorodeoxyglucose-PET, and EF scores, as well as follow-up clinical severity scores at 1 and 5 years from baseline from the Alzheimer's Disease Neuroimaging Initiative database. The correlations between EF score and regional cerebral glucose metabolism (rCMglc) were analyzed separately for aMCI with low Aβ burden (aMCI Aβ−, n=230) and aMCI with high Aβ burden (aMCI Aβ+, n=268). Multiple linear regression analysis was conducted to investigate the associations between rCMglc and clinical progression.
RESULTS
Longitudinal courses differed between aMCI Aβ− and aMCI Aβ+ groups. On average, aMCI Aβ− subjects maintained their level of clinical severity, whereas aMCI Aβ+ subjects showed progression. EF impairment in aMCI Aβ− was related to the anterior cingulate cortex (ACC), whereas that in aMCI Aβ+ was related to Alzheimer's Disease-vulnerable brain regions. ACC and the posterior cingulate cortex were associated with clinical progression in aMCI Aβ− and aMCI Aβ+, respectively.
CONCLUSION
Our findings suggest that although MCI subjects showed similar behavioral phenotypes at the time of diagnosis, EF and further progression were associated with different brain regions according to Aβ burden. Clarification of the etiologies and nature of EF impairment in aMCI are critical for disease prognosis and management.

Keyword

Mild cognitive impairment; amyloid; cognitive function; anterior cingulate cortex; posterior cingulate cortex; positron emission tomography

MeSH Terms

Alzheimer Disease
Amyloid*
Brain
Cognition
Diagnosis
Executive Function*
Follow-Up Studies
Glucose
Gyrus Cinguli
Linear Models
Metabolism
Mild Cognitive Impairment*
Neuroimaging
Phenotype
Positron-Emission Tomography
Prognosis
Amyloid
Glucose

Figure

• 

  Fig. 1 Longitudinal Clinical Dementia Rating sum of boxes (CDR-SOB) score changes according to beta-amyloid positivity. The number of subjects at baseline was 230 and 268 for amnestic mild cognitive impairment with low Aβ burden (aMCI Aβ−) and amnestic mild cognitive impairment with high Aβ burden (aMCI Aβ+), respectively. The number of subjects at 1-year follow-up (FU) was 156 and 253 for aMCI Aβ− and aMCI Aβ+, respectively. The number of subjects at 5-year FU was 52 and 68 for aMCI Aβ− and aMCI Aβ+, respectively. *p<0.01; †p<0.001.

• 

  Fig. 2 Brain areas with significant positive correlations between regional cerebral glucose metabolism and executive function in amnestic mild cognitive impairment (aMCI) with low Aβ burden. Statistical parametric maps showing positive correlations between Alzheimer's Disease Neuroimaging Initiative executive function composite scores and regional cerebral glucose metabolism using a multiple regression model with age, sex, education, and apolipoprotein E (APOE) genotype as covariates in aMCI with low Aβ burden. Significant regions have p<0.001 (uncorrected for multiple comparisons) with an extent threshold of greater than 50 contiguous voxels. The yellow-red color bar represents t-score.

• 

  Fig. 3 Brain areas with significant positive correlations between regional cerebral glucose metabolism and executive function in amnestic mild cognitive impairment (aMCI) with high Aβ burden. Statistical parametric maps showing positive correlations between Alzheimer's Disease Neuroimaging Initiative executive function composite scores and regional cerebral glucose metabolism using a multiple regression model with age, sex, education, and apolipoprotein E (APOE) genotype as covariates in aMCI with high Aβ burden. Significant regions have p<0.001 (uncorrected for multiple comparisons) with an extent threshold of greater than 50 contiguous voxels. The yellow-red color bar represents t-score.

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