naMCI Subjects Research Articles

The efficacy of gray matter atrophy and cognitive assessment in differentiation of aMCI and naMCI

Background Mild cognitive impairment (MCI) is a heterogeneous entity that can be categorized into related but different subtypes. In this study, we analyzed the gray matter structural changes of amnestic MCI (aMCI) and non-amnestic MCI (naMCI), and how it resulted in diverse cognitive impairment. Methods Altogether 77 individuals were recruited, including 28 cognitively normal controls (NC), 25 naMCI subjects, and 24 aMCI subjects. All participants underwent a 3.0 T magnetic resonance (MR) scan and a detailed neuropsychological examination. Cortical thickness and subcortical nuclei volume were extracted by Freesurfer software and compared among groups. The areas with significant differences were further analyzed by general linear regression to identify the risk factors of each cognitive impairment subtypes. Results Significant differences were observed in bilateral hippocampi, amygdala, thalamus, accumbens, left transverse temporal gyrus and left precuneus among groups. AMCI and naMCI were significantly different in the right hippocampus, bilateral amygdala, left precuneus, and left transverse temporal gyrus. Linear regression analysis revealed that the atrophy of left precuneus was a risk factor of memory, executive function (EF) and visuospatial impairment (p < 0.001). The atrophy of left amygdala, right accumbens and left thalamus were risk factors of memory, EF and language impairment respectively (p < 0.05). Conclusions These findings confirmed that different gray matter structural changes could lead to specific neuropsychological features in MCI subtypes. Thorough understanding of MCI subtypes and the underlying pathology would be beneficial for precise diagnosis and intervention.

The Differentiation of Amnestic Type MCI from the Non-Amnestic Types by Structural MRI.

Introduction: While amnestic mild cognitive impairment (aMCI) and non-amnestic mild cognitive impairment (naMCI) are theoretically different entities, only a few investigations studied the structural brain differences between these subtypes of mild cognitive impairment. The aim of the study was to find the structural differences between aMCI and naMCI, and to replicate previous findings on the differentiation between aMCI and healthy controls.Methods: Altogether 62 aMCI, naMCI, and healthy control subjects were included into the study based on the Petersen criteria. All patients underwent a routine brain MR examination, and a detailed neuropsychological examination.Results: The sizes of the hippocampus, the entorhinal cortex and the amygdala were decreased in aMCI relative to naMCI and to controls. Furthermore the cortical thickness of the entorhinal cortex, the fusiform gyrus, the precuneus and the isthmus of the cingulate gyrus were significantly decreased in aMCI relative to naMCI and healthy controls. The largest differences relative to controls were detected for the volume of the hippocampus (18% decrease vs. controls) and the cortical thickness (20% decrease vs. controls) of the entorhinal cortex: 1.6 and 1.4 in terms of Cohen's d. Only the volume of the precuneus were decreased in the naMCI group (5% decrease) compared to the control subjects: 0.9 in terms of Cohen's d. Significant between group differences were also found in the neuropsychological test results: a decreased anterograde, retrograde memory, and category fluency performance was detected in the aMCI group relative to controls and naMCI subjects. Subjects with naMCI showed decreased letter fluency relative to controls, while both MCI groups showed decreased executive functioning relative to controls as measured by the Trail Making test part B. Memory performance in the aMCI group and in the entire sample correlated with the thickness of the entorhinal cortex and with the volume of the amygdala.Conclusion: The amnestic mild cognitive impairment/non-amnestic mild cognitive impairment separation is not only theoretical but backed by structural imaging methods and neuropsychological tests. A better knowledge of the MCI subtypes can help to predict the direction of progression and create targeted prevention.

Beta-amyloid deposition and cognitive function in patients with major depressive disorder with different subtypes of mild cognitive impairment: 18F-florbetapir (AV-45/Amyvid) PET study

The objective of this study was to evaluate the amyloid burden, as assessed by (18)F-florbetapir (AV-45/Amyvid) positron emission tomography PET, in patients with major depressive disorder (MDD) with different subtypes of mild cognitive impairment (MCI) and the relationship between amyloid burden and cognition in MDD patients. The study included 55 MDD patients without dementia and 21 healthy control subjects (HCs) who were assessed using a comprehensive cognitive test battery and (18)F-florbetapir PET imaging. The standardized uptake value ratios (SUVR) in eight cortical regions using the whole cerebellum as reference region were determined and voxel-wise comparisons between the HC and MDD groups were performed. Vascular risk factors, serum homocysteine level and the apolipoprotein E (ApoE) genotype were also determined. Among the 55 MDD patients, 22 (40.0%) had MCI, 12 (21.8%) non-amnestic MCI (naMCI) and 10 (18.2%) amnestic MCI (aMCI). The MDD patients with aMCI had the highest relative (18)F-florbetapir uptake in all cortical regions, and a significant difference in relative (18)F-florbetapir uptake was found in the parietal region as compared with that in naMCI subjects (P < 0.05) and HCs (P < 0.01). Voxel-wise analyses revealed significantly increased relative (18)F-florbetapir uptake in the MDD patients with aMCI and naMCI in the frontal, parietal, temporal and occipital areas (P < 0.005). The global cortical SUVR was significantly negatively correlated with MMSE score (r = -0.342, P = 0.010) and memory function (r = -0.328, P = 0.015). The negative correlation between the global SUVR and memory in the MDD patients remained significant in multiple regression analyses that included age, educational level, ApoE genotype, and depression severity (β = -3.607, t = -2.874, P = 0.006). We found preliminary evidence of brain beta-amyloid deposition in MDD patients with different subtypes of MCI. Our findings in MDD patients support the hypothesis that a higher amyloid burden is associated with a poorer memory performance. We also observed a high prevalence of MCI among elderly depressed patients, and depressed patients with MCI exhibited heterogeneously elevated (18)F-florbetapir retention as compared with depressed patients without MCI. The higher amyloid burden in the aMCI patients suggests that these patients may also be more likely to develop Alzheimer's disease than other patients diagnosed with major depression.

Are Transversal MR Images Sufficient to Distinguish Persons with Mild Cognitive Impairment From Healthy Controls?

Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. This study aims to determine whether current standard magnetic resonance imaging (MRI) is providing markers that can distinguish between subjects with amnestic MCI (aMCI), nonamnestic MCI (naMCI), and healthy controls (HCs). A subset of 126 MCI subjects and 126 age-, gender-, and education-appropriate HCs (mean age, 70.9 years) were recruited from 4157 participants in the longitudinal community-based Heinz Nixdorf Recall Study. The burden of white matter hyperintensities (WMHs), cerebral microbleeds, and brain atrophy was evaluated on transversal MR images from a single 1.5-T MR scanner by two blinded neuroradiologists. Logistic regression and receiver-operating characteristic analysis were used for statistical analysis. Occipital WMH burden was significantly increased in aMCI, but not in naMCI relative to HCs (P = .01). The combined MCI group showed brain atrophy relative to HCs (P = .01) pronounced at caudate nuclei (P = .01) and temporal horn level (P = .004) of aMCI patients and increased at the frontal and occipital horns of naMCI patients compared to either aMCI or HCs. Microbleeds were equally distributed in the MCI and control group, but more frequent in aMCI (22 of 84) compared to naMCI subjects (3 of 23). In his cohort, increased occipital WMHs and cortical and subcortical brain atrophies at temporal horn and caudate nuclei level distinguished aMCI from naMCI subjects and controls. Volumetric indices appear of interest and should be assessed under reproducible conditions to gain diagnostic accuracy.

The Value of Cognitive Screening Tests in Patients with Amnestic and Non-amnestic MCI.

Introduction Although the original diagnostic criteria for mild cognitive impairment (MCI) highlighted the importance of memory impairment, more recently the MCI classification was expanded to encompass other cognitive domains, allowing the diagnosis of amnestic or non-amnestic MCI. Objective The primary aim of this study was to identify cognitive tests and illustrate a neuropsychological profile of cognitive subtests of persons with amnestic MCI (aMCI) and non-amnestic MCI (naMCI). Material and Methods: The study used a cross-sectional design. The study group consisted of 35 aMCI and 16 naMCI subjects matched for age, sex and years of education. The groups did not differ according to CDR. All subjects underwent a wide range of psychological tests including MMSE, TYM, DemTect, FAS, CDT, IADL and GDS. The following tests were completed to measure episodic memory, working memory, executive functions, perception and language. The analysis of variance (ANOVA) was used to analyze the differences between group means. Results The statistical analysis illustrated that total scores of MMSE, TYM, DemTect and FAS to differentiate the aMCI from naMCI subjects. Compared to naMCI, aMCI subjects scored lower in MMSE (p=0.0104) and in DemTect (p=0.0002) while they had higher scores in TYM (p=0.0067) and FAS (p=0.0427). Conclusions This study shows that cognitive screening tests provide valuable information regarding the differential diagnosis of aMCI versus naMCI. MMSE and DemTect may be seen as superior screening tests in aMCI, while TYM and FAS in naMCI subjects.

Searching for Correlations Between Results of Psychological Tests and FDG-PET as Well as Spectroscopic Metabolites From Posterior Cingulate Gyrus in Patients with MCI.

Background The aim of the study was to search for correlations between the results of psychological tests and FDG-PET as well as spectroscopic metabolites from the posterior cingulate gyrus (PCG) in patients with amnestic (aMCI) and non-amnestic MCI (naMCI). Material and Methods The study group consisted of 35 aMCI, 16 naMCI and 20 control subjects matched for age, sex and years of education. All subjects underwent a wide range of psychological tests including MMSE, CDR, TYM, DEMTEC, CDR, FAS, IADL and GDS as well neuroimaging brain studies including FDG-PET with the evaluation of glucose metabolism and magnetic resonance spectroscopy (MRS) with the evaluation of several metabolites such as NAA (neuronal marker), choline (marker of myelin turnover) and myoinositol (marker of gliosis). The results of FDG-PET and the levels of MRS metabolites obtained from PCG were compared between the subject groups and then correlated with the scores of psychological tests using Pearson’s coefficient. Results Compared to CG, both aMCI and naMCI subjects showed significantly lower levels of glucose metabolism and NAA within PCG. In the aMCI subgroup the results of FDG-PET studies revealed significant negative correlations with the scores of TYM (p=0.17, r= -0.48) while in the naMCI subgroup lower levels of NAA correlated with lower scores in DEMTEC. Conclusions In both aMCI and naMCI metabolic changes within PCG such as glucose hipometabolism and decreased neuronal activity correlate with the results of single psychological test.

White matter integrity in mild cognitive impairment: A tract-based spatial statistics study

Mild cognitive impairment (MCI) as a clinical diagnosis has limited specificity, and identifying imaging biomarkers may improve its predictive validity as a pre-dementia syndrome. This study used diffusion tensor imaging (DTI) to detect white matter (WM) structural alterations in MCI and its subtypes, and aimed to examine if DTI can serve as a potential imaging marker of MCI. We studied 96 amnestic MCI (aMCI), 69 non-amnestic MCI (naMCI), and 252 cognitively normal (CN) controls. DTI was performed to measure fractional anisotropy (FA), and tract-based spatial statistics (TBSS) were applied to investigate the characteristics of WM changes in aMCI and naMCI. The diagnostic utility of DTI in distinguishing MCI from CN was further evaluated by using a binary logistic regression model. We found that FA was significantly reduced in aMCI and naMCI when compared with CN. For aMCI subjects, decreased FA was seen in the frontal, temporal, parietal, and occipital WM, together with several commissural, association, and projection fibres. The best discrimination between aMCI and controls was achieved by combining FA measures of the splenium of corpus callosum and crus of fornix, with accuracy of 74.8% (sensitivity 71.0%, specificity 76.2%). For naMCI subjects, WM abnormality was more anatomically widespread, but the temporal lobe WM was relatively spared. These results suggest that aMCI is best characterized by pathology consistent with early Alzheimer's disease, whereas underlying pathology in naMCI is more heterogeneous, and DTI analysis of white matter structural integrity can serve as a potential biomarker of MCI and its subtypes.

Differential Hypometabolism Patterns according to Mild Cognitive Impairment Subtypes

Aims: The present study investigated cerebral glucose metabolism and structural atrophy in controls and subjects with mild cognitive impairment (MCI). Methods: The study included 13 controls, 7 MCI subjects considered as prodromal Alzheimer’s disease (MCI of the Alzheimer type, aMCI) and 7 MCI subjects having cognitive decline due to other causes, established by clinical evaluation (MCI of the non-Alzheimer type, naMCI). Glucose metabolism in the frontal, parietal and posterior cingulate cortices, the hippocampus and parahippocampal gyrus was evaluated using Statistical Parametric Mapping 2 (SPM2). Structural analysis of the whole-brain grey matter was performed with voxel-based morphometry in SPM2. Results: Significant hypometabolism was found in the medial temporal lobe in aMCI subjects compared to the controls and naMCI subjects. In addition, both the aMCI and naMCI patients had hypometabolism of the posterior cingulum relative to controls. The naMCI subjects showed atrophy of frontal and occipital areas compared to controls and aMCI patients, whereas the aMCI subjects did not show atrophy compared to the other groups. Conclusion: aMCI subjects have reduced glucose uptake levels, particularly in areas susceptible to pathological changes in Alzheimer’s disease, and the changes are more pronounced in aMCI than naMCI subjects. Our results also suggest that functional changes may be more prominent than structural changes in MCI.

IC-P1-031: 11C PiB and structural magnetic resonance imaging in Mild Cognitive Impairment

To date most cross modality comparisons with 11C Pittsburgh Compound B (PiB) have been with FDG PET. Our objective was to compare MRI and 11C PiB findings cross sectionally in subjects with Mild Cognitive Impairment (MCI). We included both amnestic MCI (aMCI, n=17) and non-amnestic MCI (naMCI, n=5). Subjects who were cognitively normal (CN, n=20) and subjects with probable Alzheimer's disease (AD, n=8) were included for reference purposes. All subjects were imaged with both 11C PiB and MRI in close temporal proximity. A global cortical PiB retention summary measure was derived from six cortical ROIs and normalized by forming a ratio with cerebellar 11C PiB retention. A cut off value of 1.5 of this ratio was used to separate subjects into those labeled “PiB positive” vs “PiB negative”. Hippocampal volumes were measured from MRI and corrected for age, gender and head size to form co-variate adjusted Z scores labeled “W scores”. All AD subjects were PiB positive and had atrophic hippocampi (Fig 1). While the majority of CN subjects were PiB negative and had no hippocampal atrophy, 6/20 CN were PiB positive. All 5 naMCI subjects were PiB negative; 3/5 had no hippocampal atrophy. Nine of 17 aMCI subjects were PiB positive and most (all but 2) also had atrophic hippocampi. Eight of 17 aMCI subjects were PiB negative and 5 of these also had atrophic hippocampi. Of the 17 aMCI subjects in the study, PiB and MRI were discordant in seven (Fig 2), and the most common discordance pattern was negative PiB with hippocampal atrophy. Most PiB positive aMCI subjects also have hippocampal atrophy and we suspect that this “AD-like” imaging profile indicates that with sufficient follow up all of these subjects will progress to AD. In contrast, we suspect that both the PiB negative aMCI subjects with atrophic hippocampi and the naMCI subjects with atrophic hippocampi have prodromal dementias other than AD, and with sufficient follow up will progress to non-AD dementias. However, this is an un proven hypothesis and longitudinal clinical follow up, preferably to autopsy, is required for confirmation.

IC-P1-038: Neuroimaging studies on Mild Cognitive Impairment and dementia in a community—implications for clinical practice: The Osaki-Tajiri Project (1)

changes in extra-temporal circuitry in amnestic MCI (aMCI), with growing evidence for disruption in parietal and frontal functionality. The concept of MCI has recently evolved to include non-amnestic syndromes (naMCI) so very little is known about functional changes in these subjects. Our objective was to compare fMRI activation in cognitively normal elderly (CN), aMCI, and naMCI subjects. Methods: Twenty-nine CN, 19 aMCI, and 12 naMCI subjects completed a blockdesign recognition memory paradigm at 3.0T. Subjects were instructed to respond to color photographs they recognized from a previous encoding task completed earlier in the same scanning session. The threshold for significance was set at p .001 (uncorrected) for within group analysis of fMRI activation using SPM2. Results: CN subjects activated a network that included the medial and lateral frontal lobes, anterior cingulate, thalamus, posterior hippocampus, fusiform gyrus, posterior cingulate, and lateral temporal-parietal-occipital lobes in a bilaterally symmetric manner (figure). Amnestic MCI subjects activated the same regions (except the thalamus) but with less magnitude. Nonamnestic MCI subjects activated the same regions as CN and aMCI (except the thalamus and posterior cingulate) but with less magnitude still than either CN or aMCI. There were no areas in which the naMCI group showed increased activation compared to aMCI. There were also no areas in which the aMCI and naMCI groups had more activation than CN. Conclusions: The network activated by a recognition memory paradigm is largely similar among CN, aMCI, and naMCI. However, the strength of activation is ordered CN aMCI naMCI. We interpret the decreased activation observed in naMCI on what is nominally a “memory” task to represent non-memory components of the task in the domains of attentional and visuospatial function. IC-P1-038 NEUROIMAGING STUDIES ON MILD COGNITIVE IMPAIRMENT AND DEMENTIA IN A COMMUNITY—IMPLICATIONS FOR CLINICAL PRACTICE: THE OSAKI-TAJIRI PROJECT (1)

IC-P1-037: Functional magnetic resonance imaging activation patterns in cognitively normal elderly, amnestic, and non-amnestic Mild Cognitive Impairment during a recognition memory task

Investigators are increasingly focusing their attention on changes in extra-temporal circuitry in amnestic MCI (aMCI), with growing evidence for disruption in parietal and frontal functionality. The concept of MCI has recently evolved to include non-amnestic syndromes (naMCI) so very little is known about functional changes in these subjects. Our objective was to compare fMRI activation in cognitively normal elderly (CN), aMCI, and naMCI subjects. Twenty-nine CN, 19 aMCI, and 12 naMCI subjects completed a block-design recognition memory paradigm at 3.0T. Subjects were instructed to respond to color photographs they recognized from a previous encoding task completed earlier in the same scanning session. The threshold for significance was set at p < .001 (uncorrected) for within group analysis of fMRI activation using SPM2. CN subjects activated a network that included the medial and lateral frontal lobes, anterior cingulate, thalamus, posterior hippocampus, fusiform gyrus, posterior cingulate, and lateral temporal-parietal-occipital lobes in a bilaterally symmetric manner (figure). Amnestic MCI subjects activated the same regions (except the thalamus) but with less magnitude. Non-amnestic MCI subjects activated the same regions as CN and aMCI (except the thalamus and posterior cingulate) but with less magnitude still than either CN or aMCI. There were no areas in which the naMCI group showed increased activation compared to aMCI. There were also no areas in which the aMCI and naMCI groups had more activation than CN. The network activated by a recognition memory paradigm is largely similar among CN, aMCI, and naMCI. However, the strength of activation is ordered CN > aMCI > naMCI. We interpret the decreased activation observed in naMCI on what is nominally a “memory” task to represent non-memory components of the task in the domains of attentional and visuospatial function.