Different Subtypes Of Mild Cognitive Impairment Research Articles

Editors' note: Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology

In response to the updated American Academy of Neurology (AAN) guidelines on mild cognitive impairment (MCI), Drs. Wang and Cui ask whether different subtypes of MCI show differences in clinical presentation that could allow for earlier prognosis. They also inquire whether more detailed recommendations on nonpharmacologic treatments in MCI, such as Tai Chi Chuan, were available. Finally, they comment that the utility of biomarkers in MCI remains uncertain. Authors Petersen et al. agree that predicting the patients with MCI who will revert to normal or remain stable is of high interest and that there are no accepted biomarkers currently. Drs. Valenzuela et al. express concern that the guidelines propose cholinesterase inhibitor treatment to be optional despite no proven benefit and the possibility of side effects. The authors explain that the wording of the recommendations reflected that some studies reviewed could not exclude a beneficial effect of cholinesterase inhibitors on MCI outcomes. They maintain that specific patient encounters should be directed by shared, informed decision-making and not guidelines. Dr. Braillon praises the AAN's updated MCI guidelines and critiques several European publications for including, in his opinion, incorrect and outdated information in their MCI recommendations. The authors express hope that the new guidelines raise awareness on several key issues regarding MCI risk factors and treatments. In response to the updated American Academy of Neurology (AAN) guidelines on mild cognitive impairment (MCI), Drs. Wang and Cui ask whether different subtypes of MCI show differences in clinical presentation that could allow for earlier prognosis. They also inquire whether more detailed recommendations on nonpharmacologic treatments in MCI, such as Tai Chi Chuan, were available.

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.

Neuroimaging of Brain Networks and Function

The human brain consists of multiple interconnected large scale networks. Recent advances in structural and functional neuroimaging techniques have introduced new concepts and approaches to noninvasively assess brain networks, which has attracted enormous research interest. To examine human brain function, traditional neuroimaging research typically focuses on localizing neural responses to varying external stimuli or task demands. However, task-induced phasic neuronal responses account for less than 5% of the brain's energy budget, while the majority of the brain's energy is used for intrinsic spontaneous brain activities. Although the number of human brain imaging studies and the knowledge obtained from these studies are growing exponentially, there are many more unanswered questions regarding the structural organization and the function of brain networks. In this special issue, we have invited a few papers that studied structural and functional brain networks using various neuroimaging methods including resting-state fMRI, diffusion tensor imaging (DTI), arterial spin labeling (ASL) perfusion MRI, functional near-infrared spectroscopy (fNIRS), magnetoencephalogram (MEG), and imaging genetics. These studies involve healthy populations as well as multiple clinical populations, including patients with cirrhosis, mild cognitive impairment (MCI) and Alzheimer's disease (AD), attention deficit hyperactivity disorder (ADHD), and epilepsy. This specific issue includes several studies focusing on clinical populations. In one study by G. Zheng and colleagues, resting-state fMRI was used to examine functional connectivity changes in the progression of minimal hepatic encephalopathy and found continuously impaired intra- and intermodular connectivity in patients with cirrhosis. In another study, Y.-Y. Wai and colleagues used tract-based spatial statistics of DTI to characterize white matter integrity in different subtypes of MCI, including amnestic MCI, dysexecutive MCI, AD, and healthy controls. They found that amnestic MCI and AD patients share significant white matter damage, whereas dysexecutive MCI patients appear to have a distinct pathogenesis. In the third study, A. dos Santos Siqueira and colleagues used graph theory and analyzed a resting-state fMRI data set from healthy children and ADHD patients in the ADHD-200 database. Distinct patterns of network dysfunction were evident for both inattentive and combined ADHD subtypes. However, the authors observed that the classification scores for discriminating between ADHD and healthy subjects were close to chance and that functional connectivity estimations were strongly dependent on the sample characteristics. In the final study, H. Zhu and colleagues used resting-state MEG to identify the epileptogenic and other abnormal regions in patients with left temporal lobe epilepsy (TLE) and provided further evidence supporting the notion that TLE is not a focal focus but a multifocus disease. A few other studies in this specific issue examined brain networks and function in normal population. In one study by H. Lei and colleagues, resting-state fMRI was integrated with genetics to examine the effect of genetic variation of the MAOA gene on resting brain activity in healthy male adolescents. Those with the low-activity MAOA genotype exhibited lower amplitude of low-frequency fluctuation (ALFF) in the pons compared to those with the high-activity MAOA genotype. Moreover, there was a significant genotype by ALFF interaction effect on impulsivity scores. In another study, H. Niu and colleagues examined the effects of learning on resting brain activity using fNIRS and demonstrated that 5 days of visual perceptual learning significantly altered resting oxygenated hemoglobin functional connectivity between visual cortex and frontal/central areas. In the study by C. Xu and colleagues, the regional homogeneity (ReHo) approach was used as an index in the resting-state fMRI to investigate gender differences in spontaneous brain activity among a large sample of young healthy adults. This study found significant ReHo differences in multiple cortical regions and resting-state networks between male and female subjects. This specific issue also includes two studies on neuroimaging methods and one review paper. In one study, X. Li and colleagues compared FAIR and PICORE sequences and systematically optimized ASL imaging parameters for measuring cerebellum grey matter and white matter perfusion. In another study, M. Gorges and colleagues demonstrated a potential framework for multiparametric functional connectivity mapping through combination of resting-state fMRI with DTI. Finally, in the review paper, T. K. Das and colleagues highlighted the structure-function relationship of the brain networks using the Ising model and graph theory. In summary, studies published in this specific issue demonstrate a few examples of continuous efforts to integrate structural and functional neuroimaging methods as well as other research modalities in order to elucidate brain networks and their function in both normal healthy population and clinical patients. Hengyi Rao Danny Jiongjiong Wang Yihong Yang Yong He

Sleep Habits in Mild Cognitive Impairment

We explored the relationship between sleep disturbances and mild cognitive impairment (MCI) in community-dwelling seniors. Recent evidence suggests that sleep habits are differentially compromised in different subtypes of MCI, but the relationship between sleep disruption and MCI remains poorly understood. We gathered daily objective measures of sleep disturbance from 45 seniors, including 16 with MCI (mean age, 86.9±4.3 y), over a 6-month period. We also collected self-report measures of sleep disturbance. Although there were no differences between groups in any of our self-report measures, we found that amnestic MCI (aMCI) volunteers had less disturbed sleep than both nonamnestic MCI (naMCI) and cognitively intact volunteers, as measured objectively by movement in bed at night (F2,1078=4.30, P=0.05), wake after sleep onset (F2,1078=41.6, P<0.001), and number of times up at night (F2,1078=26.7, P<0.001). The groups did not differ in total sleep time. In addition, the aMCI group had less day-to-day variability in these measures than the intact and naMCI volunteers. In general, the naMCI volunteers showed a level of disturbed sleep that was intermediate to that of aMCI and intact volunteers. These differences in sleep disruption between aMCI and naMCI may be related to differences in the pathology underlying these MCI subtypes.

Neuropsychological measures predict decline to Alzheimer's dementia from mild cognitive impairment.

Studies of Mild Cognitive Impairment (MCI) show elevated rates of conversion to dementia at the group level. However, previous studies of the trajectory of MCI identify great heterogeneity of outcomes, with a significant proportion of individuals with MCI remaining stable over time, changing MCI subtype classification, or reverting to a normal cognitive state at long-term follow-up. The present study examined individual outcomes at 20 months in a group of older adults classified according to MCI subtypes. A total of 106 participants, 81 with different subtypes of MCI and 25 healthy controls, undertook longitudinal neuropsychological assessment of visual and verbal memory, attentional processing, executive functions, working memory capacity, and semantic memory. At 20 months 12.3% of the MCI group progressed to dementia, 62.9% continued to meet MCI criteria, and 24.7% reverted to unimpaired levels of function. A discriminant function analysis predicted outcome at 20 months on the basis of baseline neuropsychological test performance with 86.3% accuracy. The analysis indicated that a pattern of impairments on visual episodic memory, verbal episodic memory, short-term memory, working memory, and attentional processing differentiated between participants who developed dementia, recovered from MCI, or remained in stable MCI. The results of the present study raise questions regarding the specificity of existing criteria for the subtypes of MCI, with these results indicating a high degree of instability in classification over time. In addition, the results suggest that multidomain MCI is the most reliable precursor stage to the development of AD.

The measurement of everyday cognition (ECog): Scale development and psychometric properties.

This article describes the development and validation of an instrument to assess cognitively mediated functional abilities in older adults, Everyday Cognition (ECog). The ECog is an informant-rated questionnaire comprised of multiple subscales. Confirmatory factor analysis (CFA) was used to examine its factor structure. Convergent validity was evaluated by comparing it to established measures of everyday function. External validity was evaluated by comparing ECog results across different clinical groups [cognitively normal, mild cognitive impairment (MCI), dementia]. CFA supported a seven-factor model including one global factor and six domain-specific factors (Everyday Memory, Language, Visuospatial Abilities, Planning, Organization, and Divided attention). The ECog correlated with established measures of functional status and global cognition, but only weakly with age and education. The clinical groups performed differently in each domain. In addition to the global factor, the Everyday Memory factor independently differentiated MCI from Normal, while the Everyday Language domain differentiated Dementia from MCI. Different subtypes of MCI also showed different patterns. Results suggest the ECog shows promise as a useful tool for the measurement of general and domain-specific everyday functions in the elderly.

Clinical referral patterns and cognitive profile in mild cognitive impairment

There is current interest in exploring the different subtypes of mild cognitive impairment (MCI), in terms of both their epidemiology and their cognitive profile. To examine the frequency of MCI subtypes presenting to a memory clinic and to document detailed neuropsychological profiles of patients with the amnestic subtype. Consecutive tertiary referrals (n=187) were psychiatrically evaluated; 45 patients met criteria for amnestic mild cognitive impairment (aMCI). A subgroup of 33 patients with aMCI as well as 21 healthy controls took part in a thorough neuropsychological examination. Of the patients who were examined in greater neuropsychological detail, ten had pure aMCI (none with visual memory impairment only). Fifteen met criteria for non-amnestic MCI. Fifteen had normal neuropsychological profiles. Using more than one test increased sensitivity to detect episodic memory impairment. Amnestic MCI is an important diagnosis in secondary and tertiary memory clinics. There is scope to improve the efficacy and sensitivity of the clinical assessment of this impairment.