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Aging and disease    2019, Vol. 10 Issue (4) : 711-718     DOI: 10.14336/AD.2018.0929
Orginal Article |
Anatomical Links between White Matter Hyperintensity and Medial Temporal Atrophy Reveal Impairment of Executive Functions
Takehiko Yamanaka1,4, Yuto Uchida1, Keita Sakurai2, Daisuke Kato1, Masayuki Mizuno1, Toyohiro Sato1, Yuta Madokoro1, Yuko Kondo1, Ayuko Suzuki1, Yoshino Ueki3, Fumiyasu Ishii4, Cesar V Borlongan5, Noriyuki Matsukawa1,*
1Department of Neurology,
2Department of Radiology,
3Department of Rehabilitation Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
4Department of Health Sciences, Nihon Fukushi University, Higashihaemi-chou, Aichi 475-0012, Japan.
5Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, FL 33612, USA.
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Although several studies have demonstrated correlation between white matter hyperintensities (WMH) and impairment of executive functions, the underlying anatomical-functional relationships are not fully understood. The present study sought to investigate the correlations between the volume of WMH and medial temporal lobe atrophy (MTA) using quantitative magnetic resonance image (MRI) and a variety of executive function assessments. A total of 91 patients ranging in age from 58 to 90 years with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) or early phase AD were recruited from the outpatient clinic at the Department of Neurology of Nagoya City University Hospital. We administered neuropsychological batteries evaluating verbal memory, orientation, spatial ability, sustained attention, and a variety of executive functions, including verbal fluency, flexibility, inhibition, and working memory. Quantitative MRI analyses were performed using Dr. View/Linux software and a voxel-based specific regional analysis system. Significant correlations were observed between WMH, as well as MTA, and some executive function scores. Regression analysis revealed that MTA was the strongest predictor of flexibility and verbal fluency. These findings provide new insight into the relationship between quantitative MRI analyses and various types of executive dysfunction in elderly people with MCI due to AD and/or early phase AD. When cognitive function is examined in elderly patients with MCI due to AD or early phase AD, it is important to consider the involvement of WMH and MTA, which is indicative of AD pathology in cognitive dysfunction, particularly executive function.

Keywords Alzheimer’s disease      executive function      quantitative analysis      white matter hyperintensity     
Corresponding Authors: Matsukawa Noriyuki   
About author:

These authors contributed equally to the work.

Just Accepted Date: 09 November 2018   Issue Date: 01 August 2019
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Takehiko Yamanaka
Yuto Uchida
Keita Sakurai
Daisuke Kato
Masayuki Mizuno
Toyohiro Sato
Yuta Madokoro
Yuko Kondo
Ayuko Suzuki
Yoshino Ueki
Fumiyasu Ishii
Cesar V Borlongan
Noriyuki Matsukawa
Cite this article:   
Takehiko Yamanaka,Yuto Uchida,Keita Sakurai, et al. Anatomical Links between White Matter Hyperintensity and Medial Temporal Atrophy Reveal Impairment of Executive Functions[J]. Aging and disease, 2019, 10(4): 711-718.
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Figure 1.  Quantitative analysis of white matter hyperintensity volume

A representative fluid-attenuated inversion recovery image (A). Using the bitmap statistics method in Dr. View/Linux, white matter hyperintensity volume segmentations are automatically generated (B).

Figure 2.  Correlation analyses between verbal fluency scores and imaging parameters

Significant negative correlations were confirmed with MTA (r = -0.336, p = 0.003; A) PVH (r = -0.391, p < 0.001; B) DSWMH (r = -0.311, p = 0.006; C) DSWMH-F (r = -0.288, p = 0.013; D) MTA = medial temporal lobe atrophy; PVH = periventricular hyperintensity; DSWMH = deep and subcortical white matter hyperintensity; DSWMH-F = deep and subcortical white matter hyperintensity of frontal lobe.

Number (Male / Female)91 (37 / 54)
Age (years)75.9 ± 6.3
Education (years)11.4 ± 3.1
Mini-Mental State Examination23.5 ± 4.1
Clinical Dementia Rating Scale0.6 ± 0.3
MTA Z score2.4 ± 1.1
WMH volume (cm^3)29.3 ± 23.1
PVH volume (cm^3)15.3 ± 9.9
DSWMH volume (cm^3)14.0 ± 15.5
DSWMH-F volume (cm^3)5.7 ± 6.8
Table 1  Clinical characteristics of the participants.
Cognitive function test (max score)ValueMTAPVHDSWMHDSWMH-F
Verbal Memory10WDR (10)2.5 ± 2.4-0.309**-0.228-0.028-0.069
1.5 ± 1.50.301**0.1550.1370.106
0.5 ± 0.5-0.229**0.0050.225*0.193
Sustained AttentionTMT-A79.7 ± 42.5-0.0740.367**0.443**0.353**
Executive functionsWorking MemoryDST-B3.7 ± 1.0-0.046-0.266*-0.172-0.128
InhibitionMST-B56.8 ± 31.60.0650.280*0.282*0.172
FlexibilityTMT-B/A3.4 ± 2.70.305**-0.029-0.142-0.072
Verbal FluencySVF11.2 ± 4.4-0.336**-0.391**-0.311**-0.288*
Screening of Frontal lobe functionsFAB (18)13.9 ± 2.7-0.132-0.219*-0.219*-0.180
Table 2  Correlation between cognitive performance and MRI variables.
Cognitive function test (max score)MTAPVHDSWMHDSWMH-FAgeEducation
Verbal Memory10WDR (β)-0.309**-----
OrientationADAS-J Orientation (β)0.320**-----0.392**
VisuospatialADAS-J Copy (β)-0.310**-----0.230*
Sustained AttentionTMT-A (β)--0.405**---0.379**
Executive functionsWorking MemoryDST-B (β)-----0.258*
InhibitionMST-B (β)--0.816**0.623*0.276*-0.287**
FlexibilityTMT-B/A (β)0.345**-----
Verbal FluencySVF (β)-0.290**-0.268*---0.409**
Screening of Frontal lobe functionsFAB (β)--0.215*---0.397**
Table 3  Predictive values of MRI valuables for cognitive performance.
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