Rationale and Objectives
Mild cognitive impairment has been regarded as a pre-Alzheimer condition, but some patients do not develop dementia. The authors’ objective was to determine whether findings from a combined use of H1 magnetic resonance spectroscopy (MRS), perfusion imaging (PI), and diffusion-weighted imaging (DWI) would predict conversion from amnesic mild cognitive impairment to dementia and to compare the diagnostic accuracy in discriminating patients with probable Alzheimer disease (AD), mixed dementia (MD), Lewy body dementia (LBD), pre-Alzheimer disease mild cognitive impairment (MCI), vascular MCI (VaMCI), and anxious or depression patients with cognitive impairment (DeMCI).
Materials and Methods
A longitudinal cohort of 119 consecutive and incident subjects (73 women, 46 men; age 70 ± 9.5 years) who fulfilled the criteria of amnesic MCI was followed for a mean period of 29 months. At baseline, a neuropsychological examination and standard blood test were performed, and different areas were examined by proton MRS, PI, and DWI. Among the group of patients considered to have AD, we also included patients with MD because these patients have a neurodegenerative component.
Results
After the follow-up period, 54 patients were considered as converted to dementia (49 with AD; 5 with LBD), 28 patients as MCI, 22 patients as DeMCI, and 15 patients as VaMCI. We found that N-acetylaspartate (NAA)/creatine (Cr) ratios in posterior cingulated gyri (PCG) predict the conversion to probable AD with a sensitivity of 82% and specificity of 72%, and NAA/Cr ratios in the left occipital cortex (LOC) had a sensitivity of 78% and specificity of 69%. When we used spectroscopy in the PCG and LOC to differentiate the types of MCI and dementias, we found significance differences in NAA/Cr, NAA/myoinositol (mI), NAA/choline (Cho), mI/NAA, and Cho/Cr ratios. The apparent diffusion coefficient (ADC) values in the right hippocampus showed differences in patients with LBD and DeMCI ( P = .003), LBD with MCI ( P = 0.48), and LBD and VaMCI ( P = .009).
Conclusions
NAA/Cr ratios in PCG and LOC can predict the conversion from MCI to dementia with high sensitivity and specificity. MRS can differentiate AD from MCI, but cannot differentiate the types of MCI. DWI in the right hippocampus presents higher values of ADC in LBD and allows differentiating it from MCI.
The identification of a group of people at risk of developing dementia, and Alzheimer’s disease (AD) in particular, is of major economic importance, particularly if preventive strategies or therapeutic action are to be developed. This challenge explains the popularity of the concept of mild cognitive impairment (MCI) and its wide application in the epidemiologic, clinical, paraclinical, and therapeutic domains.
The diagnostic criteria for MCI are based solely on clinical evaluation ( ). The difficulties in defining the limits of this concept and the need to characterize its different subtypes may necessitate the wider use of imaging in the future.
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Material and methods
Patients
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MRI, MRS, Diffusion MRI, and Perfusion MRI Studies
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MRI
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MRS
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Diffusion
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Perfusion
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Statistical Analysis
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Results
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Table 1
ANOVA for Different Groups (AD, DeMCI, LBD, MCI, VaMCI) with Spectroscopy
Spectroscopy ANOVA F_P_ Value LOC NAA/Cr 9.193 <.0001 NAA/mI 3.689 .007 Cho/Cr 2.825 .028 mI/NAA 3.64 .008 NAA/Cho 0.64 .64 mI/Cr 0.912 .46 PCG NAA/Cr 14.585 <.0001 NAA/mI 5.283 .001 mI/NAA 0.95 .44 NAA/Cho 5.21 .0007 Cho/Cr 0.545 .703 mI/Cr CI 1.03 .395
AD: Alzheimer’s disease; ANOVA: analysis of variance; Cho: choline; Cr: creatine; DeMCI: depression patients with mild cognitive impairment; LBD: Lewy body dementia; LOC: left occipital cortex; MCI: mild cognitive impairment; mI: myoinositol; NAA: N-acetylaspartate; PCG: posterior cingulated gyri; VaMCI: vascular mild cognitive impairment.
Table 2
ANOVA for Different Groups (AD, DeMCI, LBD, MCI, VaMCI) with Perfusion
Perfusion ANOVA F_P_ Value Right Hippocampus 0.887 .475 Occipital 1.095 .363 Temporoparietal 0.772 .546 Posterior cingulated gyrus 1.56 .191 sensitive-motor 2.1 .086 Frontal 0.944 .442 Left Hippocampus 0.,846 .499 Occipital 2.198 .074 Temporoparietal 1.363 .252 Posterior cingulated gyrus 1.763 .142 Sensitive-motor 1.97 .104 Frontal 0.818 .516
AD: Alzheimer’s disease; ANOVA: analysis of variance; DeMCI: depression patients with mild cognitive impairment; LBD: Lewy body dementia; MCI: mild cognitive impairment; VaMCI: vascular mild cognitive impairment.
Table 3
ANOVA for Differentiate Groups (AD, DeMCI, LBD, MCI, VaMCI) with Diffusion
Diffusion ANOVA F_P_ Value Right Hippocampus 4.361 .003 Temporal 1.058 .383 Occipital 0.855 .495 Caudate nucleolus 0.6 .664 Posterior cingulated gyrus 0.145 .965 Parietal white matter 0.194 .941 Frontal white matter 0.16 .958 Left Hippocampus 2.198 .076 Temporal 0.794 .532 Occipital 0.431 .786 Caudate nucleous 0.293 .882 Posterior cingulated gyrus 0.2 .937 Parietal white matter 0.276 .893 Frontal white matter 0.78 .542
AD: Alzheimer’s disease; ANOVA: analysis of variance; DeMCI: depression patients with mild cognitive impairment; LBD: Lewy body dementia; MCI: mild cognitive impairment; VaMCI: vascular mild cognitive impairment.
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Table 4
Intergroup Bonferroni Correction for Significance Statistical ANOVA Results in Spectroscopy, Diffusion, and Perfusion
ANOVA Bonferroni LOC Spectroscopy PCG Spectroscopy Diffusion NAA/Cr NAA/mI Cho/Cr mI/NAA NAA/Cr NAA/mI NAA/Cho Right Hippocampus_P_ Value_P_ Value_P_ Value_P_ Value_P_ Value_P_ Value_P_ Value_P_ Value AD DeMCI .0011 .0178 1 .0361 <.00001 .0008 .0002 .2285 LBD 1 1 1 1 .3975 1 1 .0802 MCI <.00001 .0623 .019 .0408 .0002 .0139 .1885 1 VaMCI .0033 1 .751 1 .0031 .5792 1 1 DeMCI LBD 1 .5481 1 .5441 .8524 1 .6266 .0027 MCI 1 1 .539 1 .0774 1 .4585 1 VaMCI 1 1 1 1 0,2935 1 0,4266 1 LBD MCI .9849 1 1 .7045 1 1 1 .0475 VaMCI 1 1 1 1 1 1 1 .0094 MCI VaMCI 1 1 1 1 1 1 1 1
AD: Alzheimer’s disease; ANOVA: analysis of variance; Cho: choline; Cr: creatine; DeMCI: depression patients with mild cognitive impairment; LBD: Lewy body dementia; LOC: left occipital cortex; MCI: mild cognitive impairment; mI: myoinositol; NAA: N-acetylaspartate; PCG: posterior cingulated gyri; VaMCI: vascular mild cognitive impairment.
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Table 5
Significance Statistical Receiver-operating Characteristic (ROC) Curves to Evaluate the Prediction of Conversion from MCI to Probable AD in Spectroscopy, Diffusion, and Perfusion
Test Results Area Under Curve_p_ Value Lower Bound Upper Bound Cut Point Se Sp Spectroscopy LOC NAA/Cr 0.792 <.0001 0.709 0.875 <1.57 78% 69% NAA/mI 0.672 .002 0.572 0,771 <2.47 70% 60% mI/NAA 0.681 .001 0.58 0.78 >0.40 71% 61% Cho/Cr 0.668 .002 0.569 0.767 >0.60 71% 57% PCG NAA/Cr 0.823 <.0001 0.748 0.899 <1.40 82% 72% NAA/mI 0.75 <.0001 0.657 0.842 <2.02 71% 72% mI/NAA 0.766 <.0001 0.675 0.856 >0.47 79% 67% NAA/Cho 0.679 <.0001 0.582 0.777 <2.24 70% 57%
AD: Alzheimer’s disease; ANOVA: analysis of variance; Cho: choline; Cr: creatine; DeMCI: depression patients with mild cognitive impairment; LBD: Lewy body dementia; LOC: left occipital cortex; MCI: mild cognitive impairment; mI: myoinositol; NAA: N-acetylaspartate; PCG: posterior cingulated gyri; Se: sensibility; Sp: specificity; VaMCI: vascular mild cognitive impairment.
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Discussion
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Conclusions
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