Utility of Different MR Modalities in Mild Cognitive Impairment and Its Use as a Predictor of Conversion to Probable Dementia

doi:10.1016/j.acra.2008.04.008

Academic Radiology

Volume 15, Issue 9, September 2008, Pages 1089-1098

https://doi.org/10.1016/j.acra.2008.04.008 Get rights and content

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.

Section snippets

Patients

A prospective study of 119 patients (73 women, 46 men; age 70.4 ± 9.5 years) with early cognitive impairment was conducted. These patients were recruited consecutively and prospectively at the neurology department of our hospital between October 2004 and October 2006. They had been referred by general physicians, neurologists or psychiatrists, or from other institutions. All patients underwent a diagnostic workup routinely applied in the hospital for clinical evaluation of patients with memory

Results

A total 119 patients completed the follow-up period. There were 73 women and 46 men. The average age was 70.4 ± 9.5 years. Of these 119 patients with MCI at baseline, after a mean follow-up period of 29 months (range 17–44), 54 (45.4%) were finally classified with LBD, mixed dementia, and probable AD per National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria; 28 (23.5%) were diagnosed withwith pre-AD MCI,

Discussion

Cognitive impairment has been found to be associated with different but related conditions such as in dementias, in a transitional state between normal aging and AD, and in about 38% of depressed patients (22). A British study found 11% of autopsied dementia cases had pure vascular dementia and another 20% had a combination of vascular dementia and AD (23). There is compelling evidence that vascular pathology and AD pathology are additive, and patients with a combination of both pathologies

Conclusions

In conclusion, H1-MRS of the cingulated gyrus and the occipital cortex may be a valuable tool in predicting conversion from MCI to probable AD and has proven superior to other predictors, including perfusion and diffusion MRI. Our findings should be replicated in more research. If our results are confirmed, this technique could be used for screening or prognostic purposes in patients with MCI. DWI in the right hippocampus presents higher values of ADC in LBD and allows for differentiating it

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In an evidence-based review of dementia diagnosis, the AAN did not recommend routine quantitative volumetry of the hippocampus or the entorhinal cortex because these techniques are labor intensive [9]. Diffusion-weighted imaging/apparent diffusion coefficient [35,36] and magnetization transfer imaging [37] are all either sensitive to early change or can add complementary information to atrophy measures but are second-line imaging tests. Regional cerebral blood flow determined using single-photon emission computed tomography (SPECT) imaging with Tc-99m hexamethylpropyleneamine oxime (HMPAO) shows bilateral temporoparietal or hippocampal hypoperfusion in patients with AD.
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Glutamate (Glu) is the primary excitatory neurotransmitter in the brain. Studies have shown that the ratio of N-acetylaspartate/creatine can predict with high accuracy conversion from MCI to AD [13–15]. Also increased mI/Cr and decreased NAA/Cr ratios correlated well with the severity of AD [16].
To assess the accuracy of magnetic resonance spectroscopy (1H-MRS) and brain volumetry in mild cognitive impairment (MCI) to predict conversion to probable Alzheimer's disease (AD).
Forty-eight patients fulfilling the criteria of amnestic MCI who underwent a conventional magnetic resonance imaging (MRI) followed by MRS, and T1-3D on 1.5 Tesla MR unit. At baseline the patients underwent neuropsychological examination. 1H-MRS of the brain was carried out by exploring the left medial occipital lobe and ventral posterior cingulated cortex (vPCC) using the LCModel software. A high resolution T1-3D sequence was acquired to carry out the volumetric measurement. A cortical and subcortical parcellation strategy was used to obtain the volumes of each area within the brain. The patients were followed up to detect conversion to probable AD.
After a 3-year follow-up, 15 (31.2%) patients converted to AD. The myo-inositol in the occipital cortex and glutamate + glutamine (Glx) in the posterior cingulate cortex predicted conversion to probable AD at 46.1% sensitivity and 90.6% specificity. The positive predictive value was 66.7%, and the negative predictive value was 80.6%, with an overall cross-validated classification accuracy of 77.8%. The volume of the third ventricle, the total white matter and entorhinal cortex predict conversion to probable AD at 46.7% sensitivity and 90.9% specificity. The positive predictive value was 70%, and the negative predictive value was 78.9%, with an overall cross-validated classification accuracy of 77.1%. Combining volumetric measures in addition to the MRS measures the prediction to probable AD has a 38.5% sensitivity and 87.5% specificity, with a positive predictive value of 55.6%, a negative predictive value of 77.8% and an overall accuracy of 73.3%.
Either MRS or brain volumetric measures are markers separately of cognitive decline and may serve as a noninvasive tool to monitor cognitive changes and progression to dementia in patients with amnestic MCI, but the results do not support the routine use in the clinical settings.
On the early diagnosis of Alzheimer's Disease from multimodal signals: A survey
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The number of Alzheimer's Disease (AD) patients is increasing with increased life expectancy and 115.4 million people are expected to be affected in 2050. Unfortunately, AD is commonly diagnosed too late, when irreversible damages have been caused in the patient.
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This work reviews the extensive list of psychological, physiological, behavioural and cognitive measurements that could be used for AD detection. The most promising measurements seem to be magnetic resonance imaging (MRI) for AD vs control (CTL) discrimination with an 98.95% accuracy, while electroencephalogram (EEG) shows the best results for mild cognitive impairment (MCI) vs CTL (97.88%) and MCI vs AD distinction (94.05%). Available physiological and behavioural AD datasets are listed, as well as medical imaging analysis steps and neuroimaging processing toolboxes. Some issues such as “label noise” and multi-site data are discussed.
The development of an unobtrusive and transparent AD detection system should be based on a multimodal system in order to take full advantage of all kinds of symptoms, detect even the smallest changes and combine them, so as to detect AD as early as possible. Such a multimodal system might probably be based on physiological monitoring of MRI or EEG, as well as behavioural measurements like the ones proposed along the article. The mentioned AD datasets and image processing toolboxes are available for their use towards this goal. Issues like “label noise” and multi-site neuroimaging incompatibilities may also have to be overcome, but methods for this purpose are already available.
Brain metabolism assessed via proton magnetic resonance spectroscopy in patients with amnestic or vascular mild cognitive impairment
2015, Clinical Neurology and Neurosurgery
Citation Excerpt :
Further, we investigated whether A-MCI and V-MCI are distinguishable from each other. By analyzing metabolic ratios in the posterior cingulate and left occipital cortex, Fayed et al. [39] found that MRS can differentiate MCI from AD, but cannot differentiate the subtypes of A-MCI and V-MCI. Due to the different patterns of topographical vulnerability in A-MCI and V-MCI, the choice of ROI in 1H MRS studies may lead to different outcomes.
To address the possible role of brain regional metabolic differences between different types of mild cognitive impairment (MCI).
Brain regional metabolites in patients with amnestic mild cognitive impairment (A-MCI) and vascular mild cognitive impairment (V-MCI) were measured via proton magnetic resonance spectroscopy (¹H MRS) technique. Twenty-eight patients with A-MCI, 24 patients with V-MCI and 34 normal controls (NC) were tested by a battery of neuropsychological screens. All the subjects underwent the single voxel ¹H MRS with the regions of interest (ROIs) located in the left frontal lobe, left basal ganglia and left hippocampus.
The A-MCI showed lower NAA/Cr ratio in the left hippocampus. There was a significant correlation between recent memory score and the NAA/Cr ratio. In V-MCI, NAA/Cr ratio in the left frontal lobe was positively correlated with the cognitive score evaluated with Cambridge Cognitive Examination-Chinese version (CAMCOG-C) and its subscores of orientation, praxi, language and language comprehension.
This study indicated that there are differences in metabolism related to brain regions between A-MCI and V-MCI, thus it may be concluded that ¹H MRS may be a useful tool to differentiate A-MCI and V-MCI.
ACR appropriateness criteria dementia and movement disorders
2015, Journal of the American College of Radiology
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Also, compared with PET, SPECT has lower diagnostic accuracy and is inferior in its ability to separate healthy controls from patients with true dementia [20,21]. Hydrogen-1 MRS may permit the identification of mild to moderate AD with specificity and sensitivity that suggest the potential for clinical usefulness and may predict the conversion of MCI to dementia [22]. Findings in reported studies have varied, but decreased N-acetylaspartate (NAA) and increased myoinositol with the use of the NAA/myoinositol ratio show the greatest promise [23].
Neurodegenerative disease, including dementia, extrapyramidal degeneration, and motor system degeneration, is a growing public health concern and is quickly becoming one of the top health care priorities of developed nations. The primary function of anatomic neuroimaging studies in evaluating patients with dementia or movement disorders is to rule out structural causes that may be reversible. Lack of sensitivity and specificity of many neuroimaging techniques applied to a variety of neurodegenerative disorders has limited the role of neuroimaging in differentiating types of neurodegenerative disorders encountered in everyday practice. Nevertheless, neuroimaging is a valuable research tool and has provided insight into the structure and function of the brain in patients with neurodegenerative disorders. Advanced imaging techniques, such as functional neuroimaging with MRI and MR spectroscopy, hold exciting investigative potential for better understanding of neurodegenerative disorders, but they are not considered routine clinical practice at this time.
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Higher glutamate + glutamine and reduction of N-acetylaspartate in posterior cingulate according to age range in patients with cognitive impairment and/or pain
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They are potentially specific noninvasive biomarkers of subclinical emergence of AD caused by the PSEN1 p.Glu280Ala (E280 A) mutation (37). 1H-MRS in MCI can be a predictor of cognitive decline and conversion to dementia (33), especially in MCI patients with coexisting diabetes (38). NAA levels were consistently reduced in posterior cingulate (39).
The aim of the study was to analyze 1) whether the metabolite levels in the posterior cingulate cortex (PCC) are different in healthy individuals compared to a group of patients with cognitive impairment and/or pain and 2) whether there exists a correlation between brain metabolites and the age of a patient.
Two hundred seven patients with cognitive impairment and/or pain (66 mild cognitive impairment, 54 fibromyalgia, 36 Alzheimer disease, 33 interictal migraine, 10 somatization disorder, and 8 after trigeminal neuralgia, and 193 healthy participants adjusted for gender and age. Proton magnetic resonance spectroscopy (MRS) of the brain was performed with the voxel placed in the ventral PCC and postprocessed with LCModel (Stephen Provencher, Oakville, Ontario, Canada).
Using linear regression and adjusting for gender and age, mean brain metabolite values for the pathological group, when compared to healthy controls, were significantly lower in N-acetylaspartate (P = .003) and N-acetylaspartate/creatine (P = .015) and significantly greater in glutamate + glutamine (P < .001) and glutamate + glutamine/creatine (P < .000). All metabolites were significantly correlated with age: glutamate, glutamate + glutamine, N-acetylaspartate, and their creatine ratios exhibited a negative correlation, whereas myoinositol and choline exhibited a positive correlation.
Although the number of patients is relatively small with heterogeneous state of disease, MRS in PCC may serve as a useful noninvasive tool for diagnostic of patients with cognitive impairment and pain.

View all citing articles on Scopus

¹: This work was partially supported by GE Healthcare, Madrid, Spain.

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Original investigationUtility of Different MR Modalities in Mild Cognitive Impairment and Its Use as a Predictor of Conversion to Probable Dementia1

Rationale and Objectives

Materials and Methods

Results

Conclusions

Section snippets

Patients

Results

Discussion

Conclusions

Neurobiol Aging

Neuroimaging Clin N Am

Neurobiol Aging

Lancet

Apolipoprotein E status as a predictor of the development of Alzheimer's disease in memory impaired individuals

JAMA

Definition, course, and outcome of mild cognitive impairment

Aging Neuropsiychol Cogn

Mild cognitive impairment (MCI) in medical practice: a critical review of the concept and new diagnostic procedureReport of the MCI Working Group of the European Consortium on Alzheimer's Disease

J Neurol Neurosurg Psychiatry

A critical discussion of the role of neuroimaging in mild cognitive impairment

Acta Neurol Scand Suppl

Magnetic resonance spectroscopy in AD

Neurology

Conversion from mild cognitive impairment to probable Alzheimer's disease predicted by brain magnetic resonance spectroscopy

Am J Psychiatry

Changes in metabolite ratios after treatment with rivastigmine in Alzheimer's disease: a nonrandomised controlled trial with magnetic resonance spectroscopy

CNS Drugs

Mild cognitive impairment and Alzheimer disease: regional diffusivity of water

Radiology

Perfusion MRI of the human brain with dynamic susceptibility contrast: gradient-echo versus spin-echo techniques

J Magn Reson Imaging

Dynamic susceptibility contrast MRI of regional cerebral blood volume in Alzheimer's disease

Am J Psychiatry

Mild cognitive impairment: clinical characterization and outcome

Arch Neurol

Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease

Neurology

Geriatric Depression Scale (GDS)

Co-planar stereotaxic atlas of the human brain

Functional cerebral imaging by susceptibility-contrast NMR

Magn Reson Med

Dynamic susceptibility contrast MR imaging of regional cerebral blood volume in Alzheimer disease: a promising alternative to nuclear medicine

AJNR Am J Neuroradiol

Dynamic susceptibility contrast MRI of regional cerebral blood volume in Alzheimer's disease

Am J Psychiatry

Choice of reference region in the quantification of single-photon emission tomography in primary degenerative dementia

Eur J Nucl Med

Comorbidity of mild cognitive disorder and depression—a neuropsychological analysis

Eur Arch Psychiatry Clin Neurosci

Validity of current clinical criteria for Alzheimer's disease, vascular dementia and dementia with Lewy bodies

Br J Psychiatry

Diagnosis of depression in elderly patients

Adv Psychiatr Trends

Original investigation
Utility of Different MR Modalities in Mild Cognitive Impairment and Its Use as a Predictor of Conversion to Probable Dementia1