Amnestic Mild Cognitive Impairment Group Research Articles

Learning and serial effects on verbal memory in mild cognitive impairment

ABSTRACTThe objective of this study was to examine different patterns of learning and episodic memory in 3 mild cognitive impairment (MCI) groups and a control group by administering the California Verbal Learning Test (CVLT) and using serial position effect as a principal variable. The study sample included 3 groups of patients with MCI (n = 90) divided into single-domain amnestic, multiple-domain amnestic, and multiple-domain nonamnestic MCI and a group of healthy controls (n = 60). We compared the performance of each group on several CVLT measures used in previous research, and we included a new measure that provides specific information about the serial effect. Data showed a similar pattern of learning and memory impairment in both amnestic MCI groups (i.e., no differences between the multiple-domain and single-domain subtypes); the recency effect was significantly higher in both amnestic MCI groups than in all other groups, and the primacy effect was only lower in the multiple-domain amnestic MCI subtype. Verbal learning and memory profiles of patients with amnestic MCI were very similar, independent of the presence of deficits in cognitive domains other than episodic memory. Results are discussed in light of the unitary-store model of memory.

Functional and Physical Abilities in the Early Continuum of Cognitive Decline

Background/Aims: The early cognitive continuum has been emphasized recently. We sought to characterize the functional and physical aspects of the cognitive continuum in subjects with no cognitive impairment (NCI), subjective cognitive impairment (SCI), nonamnestic (NA-MCI), and amnestic mild cognitive impairment (A-MCI). Furthermore, we identified the potential diagnostic utility of specific functional tasks. Methods: A total of 702 participants, aged ≥65 years and defined as NCI, SCI, NA-MCI, and A-MCI according to the original Petersen criteria, were included. They completed the Korean basic (K-ADL) and Instrumental Activities of Daily Living Scales (K-IADL) and the Performance-Oriented Mobility Assessment (POMA). Results: Significant differences were observed between the different cognitive status groups in three items and total scores on the K-ADL, six items and total scores on the K-IADL and POMA. Controlling for confounding factors revealed that subjects from the A-MCI group performed poorly at bathing, shopping, handling money, and the sum of assorted functional items. Conclusion: These findings demonstrated the declining feature of functional and physical performance according to the cognitive continuum, with A-MCI being discriminative with respect to specific functional tasks as compared to milder cognitive statuses. © 2014 S. Karger AG, Basel

Diagnostic transitions in mild cognitive impairment by use of simple Markov models.

Mild cognitive impairment (MCI) is a complex entity, which can involve persistence of the symptoms, conversion to dementia or improvement. The aim was to study the transitions between normal cognitive ageing and three MCI subtypes by using Markov transition models for different intervals between baseline and the follow-up assessment. A total of 294 participants over 50 years old attending primary care centres were assessed and diagnosed at baseline as multi-domain amnestic MCI (22 participants), single domain amnestic MCI (44), non-amnestic MCI (non-amnestic MCI) (26) or controls (202). We adopted an overlapping interval strategy by constructing six different mid-point time intervals according to the time between the baseline and the follow-up assessment. We used Markov transition models to study diagnostic changes in the groups in the different time intervals The rate of change was lowest in the control group. In the single domain amnestic MCI and non-amnestic MCI groups, the same diagnosis was usually retained or changed to normal cognitive functioning. In the multi-domain amnestic MCI group, the rate of transition to normal functioning was lowest, and the conversion to dementia was the highest of all groups. The best fit to the Markov models was found for the period between 18-21 months, whereas the worst fit was for the period between 9-15 months Markov models provide a comprehensive view of transitions between MCI and normal cognitive functioning. Time interval strategies seem to provide a good opportunity to monitor diagnostic transitions, although wider intervals including subsequent assessments are needed. The low rates of conversion to dementia are discussed.

Risk for Mild Cognitive Impairment Is Associated With Semantic Integration Deficits in Sentence Processing and Memory.

We examined the degree to which online sentence processing and offline sentence memory differed among older adults who showed risk for amnestic and nonamnestic varieties of mild cognitive impairment (MCI), based on psychometric classification. Participants (N = 439) read a series of sentences in a self-paced word-by-word reading paradigm for subsequent recall and completed a standardized cognitive test battery. Participants were classified into 3 groups: unimpaired controls (N = 281), amnestic MCI (N = 94), or nonamnestic MCI (N = 64). Relative to controls, both MCI groups had poorer sentence memory and showed reduced sentence wrap-up effects, indicating reduced allocation to semantic integration processes. Wrap-up effects predicted subsequent recall in the control and nonamnestic groups. The amnestic MCI group showed poorer recall than the nonamnestic MCI group, and only the amnestic MCI group showed no relationship between sentence wrap-up and recall. Our findings suggest that psychometrically defined sub-types of MCI are associated with unique deficits in sentence processing and can differentiate between the engagement of attentional resources during reading and the effectiveness of engaging attentional resources in producing improved memory.

NEUROPSYCHIATRIC SYMPTOMS IN AMNESTIC AND SUBCORTICAL VASCULAR MILD COGNITIVE IMPAIRMENT

Mild cognitive impairment (MCI) has emerged as an identifiable condition and in many cases is a transitional state preceding diagnosable Alzheimer disease (AD) and Subcortical Vascular dementia (SVaD). The aim of this study was to define the neuropsychiatric features of the amnestic MCI and compare with subcortical vascular MCI (svMCI). Patients with subcortical vascular cognitive impairment can be isolated using criteria modified from those of Erkinjunti et al. for SVaD. We used new criteria of MCI (MCI-R) subclassifying amnestic MCI.The Neuropsychiatric Inventory (NPI) was used to assess individual mean score of NPI symptoms. 155 subjects was analyzed: 115 were classified as a MCI and 40 svMCI. Subjects with subcortical vascular MCI were more compromised than those with amnestic MCI on global cognitive function. About 70% of MCI patients had some neuropsychiatric symptoms evaluated with the NPI. A significantly higher mean score of depression and anxiety has been observed in the amnestic MCI group compared with the subcortical vascular MCI group. Neuropsychiatirc symptoms occur in the majority of persons with MCI and may be the earliest manifestation of different disease. A significantly higher mean score of depression and anxiety has been observed in the amnestic MCI group compared with the subcortical vascular MCI group. These results are derived from a limited clinical sample and require confirmation in longtudinal community-based investigation.

Verbal Fluency Patterns in Mild Cognitive Impairment and Alzheimer's Disease

Background/Aims: Verbal fluency patterns can assist in differential diagnosis during neuropsychological assessment and identify individuals at risk for developing Alzheimer's disease (AD). While evidence suggests that subjects with AD perform worse on category fluency than letter fluency tasks, the pattern in mild cognitive impairment (MCI) is less well known. Methods: Performance on the Controlled Oral Word Association Test (COWAT) and Animal fluency was compared in control, amnestic MCI, non-amnestic MCI, and AD groups. The sample included 136 participants matched for age, education, and gender. Results: Both MCI groups performed similarly with a category > letter fluency pattern rather than a category < letter fluency pattern typically observed in AD. The pattern in MCI, albeit relatively more impaired than in controls, was more similar to healthy controls who exhibited a category > letter fluency pattern. Conclusion: MCI using a category < letter fluency pattern may not represent AD; however, future research requires longitudinal studies of pattern analysis.

Tract-based spatial statistics: application to mild cognitive impairment.

Rationale and Objectives. The primary objective of the current investigation was to characterize white matter integrity in different subtypes of mild cognitive impairment (MCI) using tract-based spatial statistics of diffusion tensor imaging. Materials and Methods. The study participants were divided into 4 groups of 30 subjects each as follows: cognitively healthy controls, amnestic MCI, dysexecutive MCI, and Alzheimer's disease (AD). All subjects underwent a comprehensive neuropsychological assessment, apolipoprotein E genotyping, and 3-tesla MRI. The diffusion tensor was reconstructed and then analyzed using tract-based spatial statistics. The changes in brain white matter tracts were also examined according to the apolipoprotein E ε4 status. Results. Compared with controls, amnestic MCI patients showed significant differences in the cerebral white matter, where changes were consistently detectable in the frontal and parietal lobes. We found a moderate impact of the apolipoprotein E ε4 status on the extent of white matter disruption in the amnestic MCI group. Patients with AD exhibited similar but more extensive alterations, while no significant changes were observed in dysexecutive MCI patients. Conclusion. The results from this study indicate that amnestic MCI is the most likely precursor to AD as both conditions share significant white matter damage. By contrast, dysexecutive MCI seems to be characterized by a distinct pathogenesis.

Relationship between small cerebral white matter lesions and cognitive function in patients with Alzheimer's disease and amnestic mild cognitive impairment

The main purpose of the present study was to investigate the influence of small cerebral white matter lesions on cognitive functions, and its difference by clinical stage. A total of 160 patients with Alzheimer's disease and 40 older adults with amnestic mild cognitive impairment were enrolled in the present study. The Fazekas rating scale was used for the semi-quantitative measurement of white matter lesions. Participants whose scales were more than grade 2 were excluded. Associations between the degree of small white matter lesions and cognitive functions including memory, verbal fluency, working memory, processing speed, and executive function were examined. We found that small white matter lesions influenced the performances of neuropsychological tests differently between Alzheimer's disease and amnestic mild cognitive impairment. Analysis of covariance showed significant effects of interaction on a test that assessed categorical verbal fluency. In the amnestic mild cognitive impairment group, small periventricular white matter hyperintensities were significantly associated with poor performances in categorical verbal fluency; whereas in the Alzheimer's disease group, such associations were not observed. Deep white matter hyperintensities did not influence any cognitive functions examined in both groups. The results suggested the involvement of periventricular small white matter lesions on impairment in verbal fluency, and such influence might be different depending on an individual's clinical stage.

A randomized controlled trial of multicomponent exercise in older adults with mild cognitive impairment.

BackgroundTo examine the effect of multicomponent exercise program on memory function in older adults with mild cognitive impairment (MCI), and identify biomarkers associated with improvement of cognitive functions.Methodology/Principal FindingsSubjects were 100 older adults (mean age, 75 years) with MCI. The subjects were classified to an amnestic MCI group (n = 50) with neuroimaging measures, and other MCI group (n = 50) before the randomization. Subjects in each group were randomized to either a multicomponent exercise or an education control group using a ratio of 1∶1. The exercise group exercised for 90 min/d, 2 d/wk, 40 times for 6 months. The exercise program was conducted under multitask conditions to stimulate attention and memory. The control group attended two education classes. A repeated-measures ANOVA revealed that no group × time interactions on the cognitive tests and brain atrophy in MCI patients. A sub-analysis of amnestic MCI patients for group × time interactions revealed that the exercise group exhibited significantly better Mini-Mental State Examination (p = .04) and logical memory scores (p = .04), and reducing whole brain cortical atrophy (p<.05) compared to the control group. Low total cholesterol levels before the intervention were associated with an improvement of logical memory scores (p<.05), and a higher level of brain-derived neurotrophic factor was significantly related to improved ADAS-cog scores (p<.05).Conclusions/SignificanceThe results suggested that an exercise intervention is beneficial for improving logical memory and maintaining general cognitive function and reducing whole brain cortical atrophy in older adults with amnestic MCI. Low total cholesterol and higher brain-derived neurotrophic factor may predict improvement of cognitive functions in older adults with MCI. Further studies are required to determine the positive effects of exercise on cognitive function in older adults with MCI.Trial RegistrationUMIN-CTR UMIN000003662 ctr.cgi?function = brows&action = brows&type = summary&recptno = R000004436&language = J.

Connectomics Sheds New Light on Alzheimer’s Disease

Connectomics Sheds New Light on Alzheimer’s Disease

Association between cognitive impairment and bone mineral density in postmenopausal women

This study estimated an association between cognitive impairment and bone mineral density (BMD), a surrogate marker for cumulative estrogen exposure. This cross-sectional study included 120 postmenopausal women. Based on neuropsychological tests, the women were classified into three groups: those with subjective memory impairment (SMI, n = 40), amnestic mild cognitive impairment (n = 50), and early Alzheimer disease (AD, n = 30). A complete medical history was obtained, as were the results of dual-energy x-ray absorptiometry and spine x-ray examination. BMD and the prevalence of major osteoporotic fractures were compared among the groups after adjustment for all potential confounding factors. In addition, correlations of cognitive status and BMD were tested. The SMI group was younger than either the AD or the amnestic mild cognitive impairment group. There were no significant differences among the groups with respect to other clinical characteristics. Overall, cognitive impairment was associated with lower BMD. The BMDs at both the lumbar spine and total hip were significantly lower in the AD group than in the SMI group. Regression analysis revealed that the Mini-Mental State Examination score was positively correlated and that the sum of boxes of Clinical Dementia Rating was negatively correlated with BMDs at both sites. Major osteoporotic fractures were less prevalent in the SMI group, but the difference was not statistically significant. Cognitive impairment is significantly associated with lower BMD in postmenopausal women. This finding suggests that cognitive aging is clearly multifactorial, but estrogen deficiency may be one of the contributing factors.

Anatomical and functional deficits in patients with amnestic mild cognitive impairment.

BackgroundAnatomical and functional deficits have been studied in patients with amnestic mild cognitive impairment (MCI). However, it is unclear whether and how the anatomical deficits are related to the functional alterations. Present study aims to characterize the association between anatomical and functional deficits in MCI patients.MethodsSeventeen amnestic MCI patients and 18 healthy aging controls were scanned using a T1 Weighted MPRAGE sequence and a gradient-echo echo-planar imaging sequence. Clinical severity of MCI patients was evaluated by using Clinical Dementia Rating, Mini Mental State Examination (MMSE), Clock Drawing Test, Auditory Verbal Learning Test and Activities of Daily Living. VBM with DARTEL was used to characterize the gray matter deficits in MCI. Regional amplitude of low-frequency (0.01–0.08 Hz) fluctuations (ALFF) was used to evaluate regional functional alteration in MCI and fractional ALFF(fALFF) in slow 4 (0.027–0.073 Hz) and slow 5 (0.01–0.027 Hz) were also calculated.ResultsSignificantly decreased gray matter volume (GMV) was observed in amnestic MCI group mainly in bilateral prefrontal, left temporal and posterior cingulate cortex. Significant positive correlation was observed between the GMV in left inferior frontal gyrus and MMSE scores. Interestingly, decreased ALFF/fALFF was revealed in MCI group compared to controls mainly in prefrontal, left parietal regions and right fusiform gyrus, while the increased ALFF/fALFF was found in limbic and midbrain. Furthermore, the changes of fALFF in MCI in the slow-5 band were greater than those in the slow-4. No significant correlation was found between the morphometric and functional results.ConclusionsFindings from the study document that wide spread brain volume reduction accompanied with decreased and increased regional function in MCI, while the anatomical and functional changes were independently. Therefore, the combination of structural and functional MRI methods would provide complementary information and together advance our understanding of the pathophysiology underlying the symptoms of MCI.

Amnestic Mild Cognitive Impairment: Functional MR Imaging Study of Response in Posterior Cingulate Cortex and Adjacent Precuneus during Problem-solving Tasks

To compare the blood oxygen level-dependent (BOLD) response, measured with functional magnetic resonance (MR) imaging, in the posterior cingulate cortex (PCC) and adjacent precuneus regions between healthy control subjects and patients with amnestic mild cognitive impairment (MCI) during problem-solving tasks. This study was approved by the institutional review board. Each subject provided written informed consent. Thirteen patients with amnestic MCI and 13 age- and sex-matched healthy control subjects participated in the study. The functional magnetic resonance (MR) imaging tasks were simplified 4 × 4-grid number placement puzzles that were divided into a simple task (using the row rule or the column rule to solve the puzzle) and a complex task (using both the row and column rules to solve the puzzle). Behavioral results and functional imaging results between the healthy control group and the amnestic MCI group were analyzed. The accuracy for the complex task in the healthy control group was significantly higher than that in the amnestic MCI group (P < .05). The healthy control group exhibited a deactivated BOLD signal intensity (SI) change in the bilateral PCC and adjacent precuneus regions during the complex task, whereas the amnestic MCI group showed activation. The positive linear correlations between the BOLD SI change in bilateral PCC and adjacent precuneus regions and in bilateral hippocampi in the amnestic MCI group were significant (P < .001), while in the healthy control group, they were not (P ≥ .23). These findings suggest that an altered BOLD response in amnestic MCI patients during complex tasks might be related to a decline in problem-solving ability and to memory impairment and, thus, may indicate a compensatory response to memory impairment.

A clinical memory battery for screening for amnestic mild cognitive impairment in an elderly chinese population

Amnestic mild cognitive impairment (MCI) might be more likely to progress to Alzheimer’s disease than single non-memory MCI and multiple domain MCI. After excluding those who did not conform to the inclusion criteria of amnestic MCI or healthy controls, a neuropsychologic battery that included the Mini-Mental State Examination, Clinical Dementia Rating, Chinese version of the Montreal Cognitive Assessment, Instrumental Activities of Daily Living scale and Auditory Verbal Learning Test was performed on 150 amnestic MCI and 150 normal control patients. The Chinese version of the Montreal Cognitive Assessment was measured for its test–retest reliability, sensitivity and specificity. Blood was collected for apolipoprotein E (APOE) genotyping. Compared with the control group, the amnestic MCI group performed significantly worse on all neuropsychological tests, and non-APOE-ε4 carriers in the amnestic MCI group performed better than APOE-ε4 carriers in the amnestic MCI group. The set of neuropsychological tests in our study could distinguish amnestic MCI participants from normal elderly participants accurately. APOE did have a role in amnestic MCI patients, but the magnitude and mechanism of its influence are not fully understood.

Shifting efficacy, distribution of attention and controlled processing in two subtypes of mild cognitive impairment: Response time performance and intraindividual variability on a visual search task

A visual search task was used to investigate how visual attention and intraindividual variability changes with mild cognitive impairment (MCI). Specifically, we examined the contribution of shifting efficacy, distribution of attention, and controlled processing to declines in visual attention in two groups with MCI (single-domain amnestic and multi-domain amnestic), and measured changes in intraindividual variability. Our results demonstrate that visual search performance is attenuated in multi-domain amnestic MCI, but not single-domain amnestic MCI. In addition, we found that the multi-domain amnestic MCI group was more variable than the older controls and single-domain amnestic MCI participants. These between-group differences in search efficacy and intraindividual variability increased as a function of task complexity. We attribute these decrements in performance to changes in the control of attention and shifting efficacy, but not the distribution of attention.

Episodic memory predictions in persons with amnestic and nonamnestic mild cognitive impairment

A performance-prediction paradigm was used to examine metamemory abilities in 27 individuals with amnestic mild cognitive impairment (MCI), 14 individuals with nonamnestic MCI, and 41 controls. To assess memory self-awareness, participants predicted the number of words they would remember before completing a list-learning memory task. Memory self-monitoring was evaluated by participants' ability to increase the accuracy of their predictions after experience with the list-learning task. As expected, participants with amnestic MCI demonstrated poorer memory abilities than the controls and participants with nonamnestic MCI. The amnestic MCI group also correctly predicted that they would recall less information than controls. Furthermore, both MCI groups showed accurate awareness of how differing task demands influence recall and successfully modified their memory predictions to be more accurate following task exposure. These findings revealed that individuals with amnestic and nonamnestic MCI were able to competently assess the demands of an externally driven metamemorial situation and utilize experience with a task to accurately update memory self-knowledge. Accurate metamemory skills may facilitate the ability of individuals with MCI to benefit from targeted behavioral interventions focused on utilizing compensatory strategies for everyday memory problems.

Diffusion Tensor Imaging of the Posterior Cingulate is a Useful Biomarker of Mild Cognitive Impairment

Mild cognitive impairment (MCI) is recognized as a predementia state, but its definition is inconsistent and only 20%-30% develop dementia after 2 years. Biomarkers may help identify individuals at greatest risk of progressive decline. The authors examine a novel neuroimaging technique, diffusion tensor imaging (DTI) as a potential biomarker of MCI. Cross-sectional prospective study. Subjects were recruited randomly using the electoral roll from two electorates in East Sydney, Australia. A community-dwelling sample (N = 249) and age 70-90 years. Screening to exclude dementia, comprehensive neuropsychiatric assessment, cognitive test battery, structural magnetic resonance imaging and DTI to obtain measures of fractional anisotropy (FA) and mean diffusivity (MD). MCI was diagnosed by standard criteria. After controlling for age, sex, and years of education, the amnestic MCI (aMCI) group demonstrated microstructural pathology in the parahippocampal white matter, frontal white matter, splenium of corpus callosum, and posterior cingulate region. The nonamnestic MCI (naMCI) group demonstrated microstructural pathology in the frontal white matter, internal capsule, occipital white matter, and the posterior cingulate region. A binary logistic regression model showed that DTI of the left posterior cingulate was significant in identifying persons with aMCI to an accuracy of 85.1%. Receiver operating characteristics curve analysis yielded a sensitivity of 80% and specificity of 60.3% in distinguishing aMCI from naMCI and the normal comparison group. DTI of the posterior cingulate region discriminates MCI from cognitively normal individuals with accuracy and has the potential to be used as a biomarker of MCI, in particular aMCI.

The memory alteration test (M@T) discriminates between subjective memory complaints, mild cognitive impairment and Alzheimer's disease

This work aimed at establishing the memory alteration test (M@T), which is a memory screening test, capable for discriminating between subjects with subjective memory complaints (SMC) (without objective memory impairment) and patients with amnestic mild cognitive impairment (A-MCI) and with mild Alzheimer's disease (AD). The discriminative validity was assessed in a sample of 37 subjects with SMC, 50 patients with A-MCI according to the Petersen-criteria, and 66 patients with mild AD (global deterioration scale: 4 stage) according to the NINCDS-ADRDA criteria. M@T mean scores were significantly different among groups: 39.7 ± 5.1 (±S.D.) in the SMC group, 31.5 ± 3.9 in the A-MCI group, and 21.8 ± 4.9 in mild AD. A cut-off score of 37 points had a sensitivity of 96% and a specificity of 70% to differentiate A-MCI from SMC (ABC = 0.88). A cut-off score of 33 points had a sensitivity of 100% and a specificity of 86% to differentiate mild AD from SMC sample (AUC = 0.99). We conclude that the M@T provides efficient and valid discrimination between SMC subjects and A-MCI, and between SMC subjects and mild AD.

Characterizing multiple memory deficits and their relation to everyday functioning in individuals with mild cognitive impairment.

The authors evaluated multiple memory processes and explored their contributions to everyday functional limitations in persons with mild cognitive impairment (MCI). Participants included individuals with amnestic MCI, nonamnestic MCI, and healthy older adults. As expected, the amnestic MCI group performed more poorly than the control and nonamnestic MCI groups on a content memory measure. Both MCI groups, however, performed more poorly than controls on the noncontent memory measures of prospective memory, temporal order memory, and source memory. Informants also reported that the MCI groups were experiencing greater difficulty than controls completing instrumental activities of daily living (IADLs). Noncontent memory measures were found to make an independent contribution to IADL performances over and above that of content memory. These findings demonstrate that impairments in memory beyond the traditionally assessed content memory are present in individuals with amnestic MCI and with nonamnestic MCI. The results further show that these noncontent memory processes, which have been linked with executive functioning, play a role in supporting IADLs.

Rate of entorhinal and hippocampal atrophy in incipient and mild AD: Relation to memory function

In the present study, as part of a more extensive longitudinal investigation of the in vivo anatomical markers of early and incipient AD in our laboratory, three groups of elderly participants were followed with yearly clinical evaluations and high resolution MRI scans over a 6-year period (baseline and 5 years of follow-up). At baseline, participants consisted of: (1) 35 old subjects with no cognitive impairment (controls); (2) 33 participants with amnestic mild cognitive impairment (MCI); and (3) 14 patients with very mild AD. 11 participants with amnestic MCI received a diagnosis of AD over the follow-up period and 9 controls declined in cognitive function. T1 weighted MRI scans were acquired using a 3D SPGR pulse sequence. At baseline, both the amnestic MCI and mild AD groups differed from the controls in hippocampal and entorhinal cortex volume, but not from each other. Longitudinal analyses showed that the rate of atrophy of the entorhinal cortex and hippocampus for the stable controls differed significantly from MCI participants who converted to AD and the AD groups. Furthermore, longitudinal decreases in hippocampal and entorhinal volume were related to longitudinal decline in declarative memory performance. These findings suggest that the rate of atrophy of mesial temporal lobe structures can differentiate healthy from pathological aging.