Non-amnestic Mild Cognitive Impairment Patients Research Articles

1062 GAIT SPEED AND EXECUTIVE PERFORMANCE IN PEOPLE WITH MILD COGNITIVE IMPAIRMENT

Abstract Introduction The Motoric Cognitive Risk Syndrome has highlighted the link between cognitive and motor performance, and the associated incremental higher risk of developing dementia. There is considerable debate regarding what aspects of cognition (working memory, executive function, attention) are most associated with gait changes. This study investigates the relationship between mobility scores and cognitive profiles in individuals with Mild Cognitive Impairment (MCI) specifically with regard to executive performance and amnestic/non-amnestic profiles. Method Participants diagnosed with MCI, (Clinical Dementia Rating scale global score of ≤0.5, sum of boxes score ≤ 4.0), attending a regional specialist memory service had a three-meter Timed Up and Go (TUG) gait assessment and multi-domain neuropsychiatric assessment undertaken. Amnestic neuropsychiatric profile was defined as Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) delayed memory subset score < 1SD i.e. ≤16th centile below norm for age/education. Executive function performance was assessed using the Executive Interview (EXIT-25) where higher scores reflect poorer executive performance. Results Data was reviewed for 161 patients with MCI; 53% (86/161) women. 80% (129/161) had an amnestic neuropsychiatric profile, mean age 73.8 ± 7.2 (51–94). 20% (32/161) had non-amnestic MCI, mean age 74 ± 7.07 (60–87). There was no significant difference in TUG results between amnestic and non-amnestic MCI patients (11.2 ± 3.3 vs 10.7 ± 3.1 p = NS). There was a significant increase in TUG values with worsening executive function performance [EXIT-25 score 0–9 (88/161) mean TUG = 10.5 ± 3.3 seconds vs EXIT-25 score 10–14 (43/161) mean TUG =11.9 ± 2.8 seconds vs EXIT-25 score 15–25 (30/161) mean TUG = 12.1 ± 3.9 seconds; p = 0.021] which persisted after controlling for age, gender and other relevant cofactors. Discussion Reflective of the importance of frontal lobe integration to the respective tasks, subtle differences in gait performance are associated with executive function performance regardless of predominant amnestic or non-amnestic MCI profile.

Clinical impact of 11C-Pittsburgh compound-B positron emission tomography in addition to magnetic resonance imaging and single-photon emission computed tomography on diagnosis of mild cognitive impairment to Alzheimer's disease.

This study aimed to evaluated the clinical impact of adding [11C] Pittsburgh compound-B (11C-PiB) PET for clinical diagnosis of mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia.Twenty six (mean age 78.5 ± 5.18 years, 21 females) AD (n = 7), amnestic MCI (n = 12), non-amnestic MCI (n = 3), vascular dementia, progressive supranuclear palsy (PSP) with frontotemporal dementia (FTD), FTD (n = 1 each), and normal (n = 1) patients underwent 11C-PiB-PET, MRI, and SPECT scanning. 11C-PiB-PET was compared with MRI and SPECT for clinical impact.11C-PiB-PET showed positivity in 6, 9, and 0 of the AD, amnestic MCI, and non-amnestic MCI patients, respectively, and 0 of those with another disease. Parahippocampal atrophy at VSASD was observed in 5 AD patients, 6 amnestic and PiB-positive MCI patients, 1 amnestic and PiB-negative MCI patient, and 1 vascular dementia patient. Parietal lobe hypoperfusion in SPECT findings was observed in 6, 4, and 2 of those, respectively, as well as 1 each of non-amnestic MCI, vascular dementia, and normal cases. Sensitivity/specificity/accuracy for selecting PiB-positive patients among the 15 MCI patients for 11C-PiB-PET were 100% (9/9)/100% (6/6)/100% (15/15), for VSRAD were 66.7% (6/9)/83.3% (5/6)/73.3% (11/15), and for SPECT were 44.4% (4/9)/50.0% (3/6)/46.7% (7/15), while those were 88.9% (8/9)/33.3% (2/6)/66.7% (10/15)/for combined VSRAD and SPECT. 11C-PiB-PET accuracy was significantly higher than that of SPECT.11PiB-PET alone may be useful for selecting patients who will progress from MCI to AD in the future, although follow-up study is necessary to clarify the outcome of MCI patients.

The Italian Version of the Test Your Memory (TYM-I): A Tool to Detect Mild Cognitive Impairment in the Clinical Setting.

The Test Your Memory (TYM) is a brief self-administered, cognitive screening test, currently used in several settings. It requires minimal administrator supervision and the computation of the final test score takes approximately 2 min. We assessed the discrimination ability of the Italian version of the TYM (TYM-I) in detecting Mild Cognitive Impairment (MCI) in clinical setting. TYM-I was administered to 94 MCI patients and 134 healthy controls. The clinical diagnosis of MCI was considered as the gold standard. An extended formal neuropsychological test battery was used to define MCI subtypes. Receiver Operating Characteristic (ROC) analyses were conducted to find the optimal cut-off and measure discrimination ability of TYM-I in detecting MCI. TYM-I had a similar area under the curve (AUC = 0.85) point estimate as Mini Mental State Examination (MMSE) (AUC = 0.83). A TYM-I score lower or equal to 36 was found to be optimal cut off to detect MCI. The TYM-I showed the highest discrimination ability among individuals aged more than 70 and high educational level (AUC = 0.89). The amnestic MCI subtype patients, compared to non-amnestic MCI patients, had worse performance in recall, orientation and visuospatial abilities TYM-I subscores. The TYM-I is a valid screening test in detecting cognitive dysfunction, easily carried out in clinical practice. The TYM-I subscores may allow to identify amnestic and non-amnestic MCI subtypes.

Cognitive Profiles and Atrophy Ratings on MRI in Senior Patients With Mild Cognitive Impairment.

In this cross-sectional study, we sought to describe cognitive and neuroimaging profiles of Memory clinic patients with Mild Cognitive Impairment (MCI). 51 MCI patients and 51 controls, matched on age, sex, and socio-economic status (SES), were assessed with an extensive neuropsychological test battery that included a measure of intelligence (General Ability Index, “GAI,” from WAIS-IV), and structural magnetic resonance imaging (MRI). MCI subtypes were determined after inclusion, and z-scores normalized to our control group were generated for each cognitive domain in each MCI participant. MR-images were scored by visual rating scales. MCI patients performed significantly worse than controls on 23 of 31 cognitive measures (Bonferroni corrected p = 0.001), and on 8 of 31 measures after covarying for intelligence (GAI). Compared to nonamnestic MCI patients, amnestic MCI patients had lower test results in 13 of 31 measures, and 5 of 31 measures after co-varying for GAI. Compared to controls, the MCI patients had greater atrophy on Schelten's Medial temporal lobe atrophy score (MTA), especially in those with amnestic MCI. The only structure-function correlation that remained significant after correction for multiple comparisons was the MTA—long delay recall domain. Intelligence operationalized as GAI appears to be an important moderator of the neuropsychological outcomes. Atrophy of the medial temporal lobe, based on MTA scores, may be a sensitive biomarker for the functional episodic memory deficits associated with MCI.

Association of body mass index with amnestic and non-amnestic mild cognitive impairment risk in elderly

BackgroundPrevious studies focused on the relationship between body mass index and cognitive disorder and obtained many conflicting results. This study explored the potential effects of body mass index on the risk of mild cognitive impairment (amnestic and non-amnestic) in the elderly.MethodsThe study enrolled 240 amnestic mild cognitive impairment patients, 240 non-amnestic mild cognitive impairment patients and 480 normal cognitive function controls. Data on admission and retrospective data at baseline (6 years ago) were collected from their medical records. Cognitive function was evaluated using Mini-Mental State Examination and Montreal Cognitive Assessment.ResultsBeing underweight, overweight or obese at baseline was associated with an increased risk of amnestic mild cognitive impairment (OR: 2.30, 95%CI: 1.50 ~ 3.52; OR: 1.74, 95%CI: 1.36 ~ 2.20; OR: 1.71, 95%CI: 1.32 ~ 2.22, respectively). Being overweight or obese at baseline was also associated with an increased risk of non-amnestic mild cognitive impairment (OR: 1.51, 95%CI: 1.20 ~ 1.92; OR: 1.52, 95%CI: 1.21 ~ 1.97, respectively). In subjects with normal weights at baseline, an increased or decreased body mass index at follow-up was associated with an elevated risk of amnestic mild cognitive impairment (OR: 1.80, 95%CI: 1.10 ~ 3.05; OR: 3.96, 95%CI: 2.88 ~ 5.49, respectively), but only an increased body mass index was associated with an elevated risk of non-amnestic mild cognitive impairment (OR: 1.71, 95%CI: 1.16 ~ 2.59).ConclusionsUnhealthy body mass index levels at baseline and follow-up might impact the risk of both types of mild cognitive impairment (amnestic and non-amnestic).

AMNESTIC MILD COGNITIVE IMPAIRMENT: ASSOCIATED FACTORS WITH REMISSION TO NORMAL COGNITION IN A SAMPLE OF BRAZILIAN ELDERLY WITH LOW EDUCATIONAL LEVEL

Mild cognitive impairment (MCI) is an intermediate condition between a normal cognition and dementia. The average remission rate from MCI to normal cognition is about 2.1% to 53% per year. However, there are no study evaluating remission rate in the Brazilian MCI population and neither the associated factors to this type of evolution. Our aim was to determine the remission rate from MCI to normal cognition and evaluate the clinical and demographic factors related to it. We conducted a cohort of individuals with aMCI and controls with normal cognition aged over 60 years which were recruited between 2010 and 2015. The participants were annually evaluated by geriatricians and neuropsychologists trained in cognitive assessment. The categorical dates were analyzed by chi-squared test and Fisher test and means comparison by T student, Anova, Mann Whiney e Kruskal-wallis tests. Kaplan-Meier survive curve was performed. Risk factors were evaluated using binary logistic regression analysis or linear regression analysis. We used the statistical package SPSS version 20.0 (IBM®). Out of 306 individuals initially recruited for inclusion criteria, only 176 participants were selected (51 were in the control group, 112 in amnestic group and 13 in non-amnestic group), with mean age of 75.51±7.26 years, 69.9% female, all had 4.10±3.41 years of education. Remission occurred in 14.3% of the 112 aMCI patients and in 30.8% of the 13 non-amnestic MCI patients. By means of multivariate analysis, the associated factors with the remission from aMCI to normal cognition were age [RR: 0.907 (95% CI: 0.849 − 0.969), p value: 0.004], Geriatric Depression Scale − 15 item version (GDS-15) [RR: 0.733 (95% CI: 0.553 − 0.972), p value: 0.031], list of words from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) – subtopic evocation [RR: 1.492 (95% CI: 1.038 − 2.144), p value: 0.031] and mini-mental state examination (MMSE) [RR: 1.273 (95% CI: 1.048 − 1.548), p value: 0.015]. After mean period of 2.5 years, the remission ratio was 14.3% in the group with aMCI. GDS-15, list of words from the CERAD – subtopic evocation and MMSE were associated with remission from aMCI to normal cognition.

Exploring the Phenotype in Mild Cognitive Impairment to Aid the Prediction of Those at Risk of Transitioning to Parkinson Disease and Dementia With Lewy Bodies.

To date, only limited research has concurrently investigated the presence of rapid eye movement sleep behavior disorder (RBD) and other features associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB) in people presenting with mild cognitive impairment (MCI). As a first step towardsa longitudinal research project, the present study explored the relationships between MCI, RBD, and depression in 108 older adults who presented with subjective memory complaints but were not known to have a neurodegenerative condition. The present study found that RBD was a frequent feature in individuals with MCI (35%). Furthermore, MCI patients with RBD were more likely to exhibit nonamnestic MCI (89%) rather than an amnestic MCI phenotype (χ2 = 4.99, P = .025). Specifically, nonamnestic MCI patients with RBD had selective deficits in executive function and verbal memory, as well as a higher level of depressive symptoms. This cognitive and psychiatric profile is aligned with PD and DLB patientsat their time of initial diagnosis and suggests that targeting nonamnestic MCI patients who report RBD with additional biomarker testing including smell, color vision, and neuroimaging (eg, dopamine transporters scan and transcranial ultrasonography) may aid in early diagnosis and prediction of these α-synucleinopathies.

Diagnostic role of 11C-Pittsburgh compound B retention patterns and glucose metabolism by fluorine-18-fluorodeoxyglucose PET/CT in amnestic and nonamnestic mild cognitive impairment patients.

Amyloid imaging clinically is usually reported as positive or negative, and the role of amyloid topography has not been studied before. To evaluate in a clinical setting the regional distribution patterns of C-Pittsburgh compound B (C-PIB) and the fluorine-18-fluorodeoxyglucose (F-FDG) uptake in patients with mild cognitive impairment (MCI), we designed this study. We studied 81 consecutive MCI patients, 64 amnestic (A-MCI) and 17 nonamnestic (NA-MCI) by C-PIB and F-FDG PET/computed tomography, by visual analysis. PIB retention was classified according to the regional distribution into the following patterns: A (frontal, lateral temporal, basal ganglia and anterior cingulate) and B (global retention). F-FDG images were considered positive only if temporoparietal hypometabolism consistent with Alzheimer's disease was observed. In 42 of the 64 A-MCI, C-PIB was positive. Twelve of the 42 positive A-MCI showed an A-pattern, all F-FDG negative, and 30 a B-pattern, 10 F-FDG positive and 20 F-FDG negative. Of the 17 NA-MCI, C-PIB was positive in three and F-FDG was positive in one. The different proportion of C-PIB positivity in A-MCI and NA-MCI was highly significant (P<0.001). Two different C-PIB patterns were observed in MCI patients and for the A-pattern, glucose hypometabolism consistent with Alzheimer's disease is highly unlikely. These findings may contribute towards a better selection of patients for future potential treatments and also to optimize the use of F-FDG-PET/CT.

Salience network and parahippocampal dopamine dysfunction in memory-impaired Parkinson disease.

Patients with Parkinson disease (PD) and mild cognitive impairment (MCI) are vulnerable to dementia and frequently experience memory deficits. This could be the result of dopamine dysfunction in corticostriatal networks (salience, central executive networks, and striatum) and/or the medial temporal lobe. Our aim was to investigate whether dopamine dysfunction in these regions contributes to memory impairment in PD. We used positron emission tomography imaging to compare D2 receptor availability in the cortex and striatal (limbic and associative) dopamine neuron integrity in 4 groups: memory-impaired PD (amnestic MCI; n = 9), PD with nonamnestic MCI (n = 10), PD without MCI (n = 11), and healthy controls (n = 14). Subjects were administered a full neuropsychological test battery for cognitive performance. Memory-impaired patients demonstrated more significant reductions in D2 receptor binding in the salience network (insular cortex and anterior cingulate cortex [ACC] and the right parahippocampal gyrus [PHG]) compared to healthy controls and patients with no MCI. They also presented reductions in the right insula and right ACC compared to nonamnestic MCI patients. D2 levels were correlated with memory performance in the right PHG and left insula of amnestic patients and with executive performance in the bilateral insula and left ACC of all MCI patients. Associative striatal dopamine denervation was significant in all PD patients. Dopaminergic differences in the salience network and the medial temporal lobe contribute to memory impairment in PD. Furthermore, these findings indicate the vulnerability of the salience network in PD and its potential role in memory and executive dysfunction.

Amyloid imaging with 11C-PIB PET/CT and glucose metabolism with 18F-FDG PET/CT in a study on cognitive impairment in the clinical setting

The objective of this study was to evaluate the contribution of amyloid imaging with (11)C-Pittsburgh compound B ((11)C-PIB) and of glucose metabolism on F-fluorodeoxyglucose ((18)F-FDG) PET/CT to the study of cognitive impairment in the clinical setting. Thirty-four patients (15 male, 19 female) were enrolled in the study. They were classified according to their clinically presented symptoms. Six patients had subjective memory complaints, five had nonamnestic mild cognitive impairment (MCI), seven had amnestic MCI, seven had prodromal Alzheimer's disease (AD), five had frontotemporal dementia, two had dementia with Lewy bodies, and two had cortical degeneration. All the scans were conducted to determine the likelihood of AD or to differentiate between AD and other dementia. Static 30-min (11)C-PIB and 15-min (18)F-FDG PET/CT scans were obtained. A visual analysis of images was performed. Three of the six patients with subjective memory complaints had positive (11)C-PIB scans and one of them also had (18)F-FDG hypometabolism. All five nonamnestic MCI patients had normal (11)C-PIB and (18)F-FDG. Four of the seven amnestic MCI patients showed (11)C-PIB cortical retention but only one had positive (18)F-FDG. Positive (11)C-PIB and (18)F-FDG were detected in five of the seven prodromal AD patients. All the five patients with FDT had positive (18)F-FDG scans, but only one of the five had (11)C-PIB cortical retention. Both dementia with Lewy bodies and cortical degeneration patients had positive (11)C-PIB and (18)F-FDG scans. The combined use of (11)C-PIB and (18)F-FDG PET provides relevant information for the clinical management of cognitive impairment. The detection of positive (11)C-PIB cortical retention in patients may be an indicator of the need for further clinical assessment and monitoring.

Risk Factors for Behavioral Abnormalities in Mild Cognitive Impairment and Mild Alzheimer's Disease

Background: Behavioral symptoms are common in both mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods: We analyzed the Neuropsychiatric Inventory Questionnaire data of 3,456 MCI and 2,641 mild AD National Alzheimer's Coordinating Center database participants. Using factor analysis and logistic regression we estimated the effects of age, sex, race, education, Mini-Mental State Examination, functional impairment, marital status and family history on the presence of behavioral symptoms. We also compared the observed prevalence of behavioral symptoms between amnestic and nonamnestic MCI. Results: Four factors were identified: affective behaviors (depression, apathy and anxiety); distress/tension behaviors (irritability and agitation); impulse control behaviors (disinhibition, elation and aberrant motor behavior), and psychotic behaviors (delusions and hallucinations). Male gender was significantly associated with all factors. Younger age was associated with a higher prevalence of distress/tension, impulse control and psychotic behaviors. Being married was protective against psychotic behaviors. Lower education was associated with the presence of distress/tension behaviors. Caucasians showed a higher prevalence of affective behaviors. Functional impairment was strongly associated with all behavioral abnormalities. Amnestic MCI patients had more elation and agitation relative to nonamnestic MCI patients. Conclusions: Younger age, male gender and greater functional impairment were associated with higher overall presence of behavioral abnormalities in MCI and mild AD. Marital status, lower education and race had an effect on selected behaviors.

Serial Position Effects in Patients with Mild Cognitive Impairment and Early and Moderate Alzheimer's Disease Compared with Healthy Comparison Subjects

Background/Aims: This study aimed to investigate whether the serial position effects in memory can differentiate patients with different subtypes of mild cognitive impairment (MCI) from healthy controls and patients with different stages of Alzheimer's disease (AD). Methods: The serial position effects was tested with the CERAD word list task in 184 persons (39 healthy control subjects, 15 amnestic MCI single domain subjects, 23 amnestic MCI multiple domain subjects, 31 nonamnestic MCI subjects, 45 early or mild AD patients, and 31 moderate AD patients). Results: With progression of dementia, memory deficits increased and the impairment in the primacy effect during the learning trials advanced, whereas the recall of recent items was less impaired. The serial position profile of nonamnestic MCI patients resembled that of healthy control subjects, whereas amnestic MCI patients showed poorer performance in all 3 positions but no significant difference as a function of serial word position. Conclusion: Analyses of the serial position effect may be a useful complement to clinical neuropsychological measures for distinguishing amnestic MCI patients from normal aging and patients with different stages of dementia.

White Matter Abnormalities and Structural Hippocampal Disconnections in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease

The purpose of this project was to evaluate white matter degeneration and its impact on hippocampal structural connectivity in patients with amnestic mild cognitive impairment, non-amnestic mild cognitive impairment and Alzheimer’s disease. We estimated white matter fractional anisotropy, mean diffusivity and hippocampal structural connectivity in two independent cohorts. The ADNI cohort included 108 subjects [25 cognitively normal, 21 amnestic mild cognitive impairment, 47 non-amnestic mild cognitive impairment and 15 Alzheimer’s disease]. A second cohort included 34 subjects [15 cognitively normal and 19 amnestic mild cognitive impairment] recruited in Montreal. All subjects underwent clinical and neuropsychological assessment in addition to diffusion and T1 MRI. Individual fractional anisotropy and mean diffusivity maps were generated using FSL-DTIfit. In addition, hippocampal structural connectivity maps expressing the probability of connectivity between the hippocampus and cortex were generated using a pipeline based on FSL-probtrackX. Voxel-based group comparison statistics of fractional anisotropy, mean diffusivity and hippocampal structural connectivity were estimated using Tract-Based Spatial Statistics. The proportion of abnormal to total white matter volume was estimated using the total volume of the white matter skeleton. We found that in both cohorts, amnestic mild cognitive impairment patients had 27-29% white matter volume showing higher mean diffusivity but no significant fractional anisotropy abnormalities. No fractional anisotropy or mean diffusivity differences were observed between non-amnestic mild cognitive impairment patients and cognitively normal subjects. Alzheimer’s disease patients had 66.3% of normalized white matter volume with increased mean diffusivity and 54.3% of the white matter had reduced fractional anisotropy. Reduced structural connectivity was found in the hippocampal connections to temporal, inferior parietal, posterior cingulate and frontal regions only in the Alzheimer’s group. The severity of white matter degeneration appears to be higher in advanced clinical stages, supporting the construct that these abnormalities are part of the pathophysiological processes of Alzheimer’s disease.

False Recognition Helps to Distinguish Patients with Alzheimer’s Disease and Amnestic MCI from Patients with Other Kinds of Dementia

Two recent reviews on neuropsychological assessment argue that Alzheimer’s disease (AD) is characterized by deficits in delayed recall and that this allows differentiating AD from other types of dementia. We attempted to differentiate patients with AD and amnestic mild cognitive impairment (MCI) from patients with fronto-subcortical dementia, normal pressure hydrocephalus and vascular dementia using a simple picture recognition task. We examined 130 patients, 89 with dementia and 41 with MCI. The combination of the CERAD-NP savings score and the number of false recognitions yielded a sensitivity of 100% for identifying AD patients. Moreover, adding the score for false recognitions to that of delayed recall improved the specificity of the diagnosis from 50% to 90%. After matching the groups on memory performance, the AD group still produced more false recognitions. The results suggest that delayed recall impairment and recognition errors stem from different sources. We also found that the number of false recognitions differs between amnestic and non-amnestic MCI patients. The quality of the differential diagnosis may therefore be enhanced significantly by taking into account both delayed recall and false recognitions provoked by a picture recognition task.

Outcome in subgroups of mild cognitive impairment (MCI) is highly predictable using a simple algorithm

Although it is well recognized that MCI represents a risk state for subsequent dementia, estimates of conversion vary widely according to the diagnostic criteria employed. There are currently no simple cognitive predictors of high and low risk of progression. We followed 107 non-demented non-depressed subjects from an original cohort of 124--sub-classified as follows: pure amnestic MCI (22), multi-domain MCI (54), non-amnestic MCI (10) and worried well (21). At 2 years, outcome varied considerably. Of the multi-domain MCI group 59% progressed to dementia and only 5% improved. By contrast, in pure amnestic MCI only 18% progressed and 41% improved. Of non-amnestic MCI patients 70% improved. The best predictor of progression was a combination of the Addenbrooke's cognitive examination (ACE) and the paired associate learning task (PAL), which produced high negative predictive (90%) and sensitivity (94%) values. The results indicate very different outcomes according to whether patients have pure amnestic versus multi-domain MCI. While the latter is an aggressive disorder, the former is more benign and unstable even in a clinic setting. Patients with scores >88 on the ACE and/or <14 errors on the PAL can be confidently reassured of a good prognosis.

Plasma Levels of Monocyte Chemotactic Protein 3 and Beta-Nerve Growth Factor Increase with Amnestic Mild Cognitive Impairment

A number of studies have investigated peripheral inflammatory indices, including plasma cytokines and related molecules according to subtypes of dementia, but not in mild cognitive impairment (MCI). In this study, we used multiplex cytokine assay to assess the plasma levels of 22 cytokines in patients with MCI subtyped as amnestic and non-amnestic, according to cognitive features. When comparing the levels of plasma growth factors, chemokines and cytokines, plasma levels of monocyte chemotactic protein 3 (MCP-3), and beta-nerve growth factor (beta-NGF) in these two groups, they were found to be significantly higher in amnestic MCI patients than in non-amnestic MCI patients, after adjusting for age and gender. This suggests that plasma MCP-3 and beta-NGF may be useful in differentiating subtypes of MCI.

IC-P1-009: Patterns of cerebral hypoperfusion in amnestic and dysexecutive MCI subgroups

Background: Few studies on mild cognitive impairment (MCI) have examined non-amnestic MCI patients. The objective of this study was to compare MRI measurements of resting state cerebral perfusion in two subgroups of MCI patients. Specifically, patients with dysexecutive MCI (dMCI), operationally defined as individuals with report of recent onset of dysexecutive symptoms (e.g., attention, multi-tasking, behavior) and/or had impaired scores on executive, but not memory, measures (N 17), patients with amnestic MCI (aMCI), who had impaired memory, but not executive function (N 18), and cognitively normal elderly controls (N 25). Methods: All subjects underwent arterial spin-labeling and structural MR imaging. Perfusion images were analyzed on a voxel-by-voxel basis and thresholded at an uncorrected voxel-level p-value of 0.001 and a cluster size of 10 voxels with SPM2. Results: Relative to controls, dMCI patients showed hypoperfusion in the right middle frontal cortex, while aMCI patients showed hypoperfusion in the left middle frontal cortex and right precuneus. Compared to dMCI, aMCI patients showed hypoperfusion in the right precuneus and middle cingulum bilaterally. Compared to aMCI, dMCI patients showed hypoperfusion in the right frontal lobe, near the precentral gyrus when we used a more liberal voxel-level threshold of p 0.003. We also examined correlations between cognition, function, and resting state cerebral perfusion. Better Trail-making scores (a measure of executive function) correlated with greater resting state cerebral perfusion in the middle frontal cortex, bilaterally in controls, in the precentral gyrus in aMCI patients, and in the left cuneus and right parietal cortex in dMCI patients. Lower scores on the Functional Activities Questionnaire (indicating less functional dependence) correlated with greater resting state perfusion in the right postcentral gyrus, left inferior and superior frontal cortex in aMCI patients and in the right cuneus, left precuneus, and right superior temporal lobe in dMCI patients. Conclusions: The finding that aMCI and dMCI patients exhibited different spatial patterns of cerebral hypoperfusion supports the existence of two distinct subgroups of MCI. Furthermore, these results suggest that resting cerebral perfusion in the less affected brain regions (i.e., frontal cortex in aMCI, posterior cortex in dMCI) is related to cognition and function in MCI patients.

Mini-mental State Examination performance in mild cognitive impairment subtypes

Diagnosis of mild cognitive impairment (MCI) and its subtypes requires a detailed diagnostic assessment and so may be missed at routine primary-care appointments, since the ordinary dementia screening tests lack sensitivity owing to ceiling effects, especially in highly educated subjects. The study was undertaken using a cross-sectional assessment of 112 elderly subjects (mean age 67.96+/-5.77 years, and mean education level of 12.8+/-5.7 years) with a semi-structured interview and a neuropsychological battery. MCI patients did not differ from controls on total MMSE scores (p=0.212). Nevertheless, MCI patients showed worse performance than controls on the verbal memory task (p=0.012), and "drawing a pentagon" (p=0.03). Amnestic MCI patients performed worse only on the "three-word recall" task (p=0.013); non-amnestic MCI patients performed worse on the "three-stage command" task (p=0.001); and multiple-domain MCI patients performed worse on the "drawing a pentagon" task (p=0.001) and had a trend toward performing poorly on the 'three word recall' task (p=0.06). The analysis of MMSE subtest scores, in addition to MMSE total scores, may increase the sensitivity of the MMSE test in screening for MCI and its subtypes.