Mild Cognitive Impairment Subtypes Research Articles

Mild cognitive impairment in Parkinson's disease: the Parkinson's disease cognitive study (PACOS).

Approximately 30% of Parkinson's disease (PD) patients show impaired cognitive performance, which is suggestive of Mild Cognitive Impairment (MCI), representing a predictor of dementia, especially when present at diagnosis. The objective of the study was to evaluate the frequency and clinical predictors of MCI in a large hospital-based cohort of PD patients. We collected cross-sectional data from the Parkinson's disease cognitive impairment study (PACOS), a multicenter study involving two Movement Disorder centers, which are located in south Italy. The PD subjects were diagnosed according to the UK Brain Bank criteria and they underwent an extensive neuropsychological assessment. PD-MCI was diagnosed according to the Movement Disorder Society task force criteria for MCI. PD severity was evaluated in accordance with theUnified PD Rating Scale-Motor Examination (UPDRS-ME) and the Hoehn and Yahr scales. The study included 659 PD patients (57.5% men; mean age 67.0±9.7years), with a mean disease duration of 3.8±4.6years and a mean UPRDS-ME score of 25.8±12.3. PD-MCI was diagnosed in 261 (39.6%) subjects and in 82 (31.7%) of 259 newly diagnosed patients (disease duration≤1year). An amnestic MCI multidomain phenotype was the most frequent MCI subtype (39.1% of the overall sample and 43.9% in newly diagnosed PD). A positive significant association between MCI, age and motor scores was found at multivariate logistic regression analysis, while a negative association was observed between educational level and MCI. In conclusion and in agreement with the literature data, the prevalence of MCI recorded in the PACOS sample was approximately 40 and 32% amongst newly diagnosed patients.

Increased Amplitude of the P3a ERP Component as a Neurocognitive Marker for Differentiating Amnestic Subtypes of Mild Cognitive Impairment.

The event-related potential (ERP) technique has been shown to be useful for evaluating changes in brain electrical activity associated with different cognitive processes, particularly in Alzheimer’s disease (AD). Longitudinal studies have shown that a high proportion of people with amnestic mild cognitive impairment (aMCI) go on to develop AD. aMCI is divided into two subtypes according to the presence of memory impairment only (single-domain aMCI: sdaMCI) or impairment of memory and other cognitive domains (multi-domain aMCI: mdaMCI). The main aim of this study was to examine the effects of sdaMCI and mdaMCI on the P3a ERP component associated with the involuntary orientation of attention toward unattended infrequent novel auditory stimuli. Participants performed an auditory-visual distraction-attention task, in which they were asked to ignore the auditory stimuli (standard, deviant, and novel) and to attend to the visual stimuli (responding to some of them: Go stimuli). P3a was identified in the Novel minus Standard difference waveforms, and reaction times (RTs) and hits (in response to Go stimuli) were also analyzed. Participants were classified into three groups: Control, 20 adults (mean age (M): 65.8 years); sdaMCI, 19 adults (M: 67 years); and mdaMCI, 11 adults (M: 71 years). In all groups, the RTs were significantly longer when Go stimuli were preceded by novel (relative to standard) auditory stimuli, suggesting a distraction effect triggered by novel stimuli; mdaMCI participants made significantly fewer hits than control and sdaMCI participants. P3a comprised two consecutive phases in all groups: early-P3a (e-P3a), which may reflect the orienting response toward the irrelevant stimuli, and late-P3a (l-P3a), which may be a correlate of subsequent evaluation of these stimuli. The e-P3a amplitude was significantly larger in mdaMCI than in sdaMCI participants, and the l-P3a amplitude was significantly larger in mdaMCI than in sdaMCI and Control participants, indicating greater involuntary capture of attention to unattended novel auditory stimuli and allocation of more attentional resources for the subsequent evaluation of these stimuli in mdaMCI participants. The e-P3a and l-P3a components showed moderate to high sensitivity and specificity for distinguishing between groups, suggesting that both may represent optimal neurocognitive markers for differentiating aMCI subtypes.

Discriminating Subtypes of Mild Cognitive Impairment according to Performance on Semantic Verbal Fluency Tasks with Different Administration Time

Discriminating Subtypes of Mild Cognitive Impairment according to Performance on Semantic Verbal Fluency Tasks with Different Administration Time

Long-Term Cognitive Impairment after Hospitalization for Community-Acquired Pneumonia: a Prospective Cohort Study.

Recent studies suggest older patients hospitalized for community-acquired pneumonia are at risk for new-onset cognitive impairment. The characteristics of long-term cognitive impairment after pneumonia, however, have not been elucidated. To characterize long-term cognitive impairment among adults of all ages hospitalized for community-acquired pneumonia. Prospective cohort study. Adults without severe preexisting cognitive impairment who were hospitalized with community-acquired pneumonia. At enrollment, we estimated baseline cognitive function with the Short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). At 2- and 12-month follow-up, we assessed cognition using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and tests of executive function, diagnosing cognitive impairment when results were ≥ 1.5 standard deviations below published age-adjusted means for the general population. We also identified subtypes of mild cognitive impairment using standard definitions. We assessed 58 (73%) of 80 patients who survived to 2-month follow-up and 57 (77%) of 74 who survived to 12-month follow-up. The median [range] age of survivors tested was 57 [19-97] years. Only 8 (12%) had evidence of mild cognitive impairment at baseline according to the Short IQCODE, but 21 (38%) at 2months and 17 (30%) at 12months had mild cognitive impairment per the RBANS. Moderate-to-severe cognitive impairment was common among adults ≥ 65years [4/13 (31%) and 5/13 (38%) at 2 and 12months, respectively] but also affected many of those < 65years [10/43 (23%) and 8/43 (19%) at 2 and 12months, respectively]. Deficits were most often noted in visuospatial function, attention, and memory. A year after hospitalization for community-acquired pneumonia, moderate-to-severe impairment in multiple cognitive domains affected one-third of patients ≥ 65years old and 20% of younger patients, and another third of survivors had mild cognitive impairment.

Association between Frontal-Executive Dysfunction and Speech-in-Noise Perception Deficits in Mild Cognitive Impairment.

Background and PurposeSpeech-in-noise perception deficits have been demonstrated in patients with mild cognitive impairment (MCI). However, it remains unclear whether the impairment of speech perception varies between MCI subtypes. The purpose of this study was twofold: 1) to compare speech perception performance among MCI subgroups, and 2) to identify the cognitive domains specifically related to speech-in-noise perception.MethodsWe studied 46 patients with MCI and 39 hearing-threshold-matched cognitively normal elderly (CNE) subjects. Two different patient classifications were used: 1) patients with amnestic mild cognitive impairment (aMCI) (n=21) or nonamnestic mild cognitive impairment (naMCI) (n=25), and 2) patients with frontal-executive dysfunction (FED) (n=16) or without FED (n=30). All of the subjects underwent audiometric, neuropsychological, and speech perception assessments. Speech-in-noise perception was measured using sentence recognition tests in the presence of two types of background noise at four levels.ResultsFirst, as the level of background noise increased, the MCI with FED group scored lower than both the MCI without FED and CNE groups under both types of noise. Second, both the naMCI and aMCI groups scored lower than the CNE group, but there were no differences between the naMCI and aMCI groups in sentence recognition under any noise conditions. Third, significant correlations were found between sentence recognition and executive function scores both in the MCI groups and in the CNE group.ConclusionsOur findings suggest that frontal-executive function is strongly related to speech-in-noise perception and that MCI patients with FED have greater deficits in speech-in-noise perception compared to other subgroups of MCI.

Better prognostic accuracy in younger mild cognitive impairment patients with more years of education

IntroductionAge and years of education influence the risk of dementia and may impact the prognostic accuracy of mild cognitive impairment subtypes. MethodsMemory clinic patients without dementia (N = 358, age 64.0 ± 7.9) were stratified into four groups based on years of age (≤64 and ≥65) and education (≤12 and ≥13), examined with a neuropsychological test battery at baseline and followed up after 2 years. ResultsThe prognostic accuracy of amnestic multi-domain mild cognitive impairment for dementia was highest in younger patients with more years of education and lowest in older patients with fewer years of education. Conversely, conversion rates to dementia were lowest in younger patients with more years of education and highest in older patients with fewer years of education. DiscussionMild cognitive impairment subtypes and demographic information should be combined to increase the accuracy of prognoses for dementia.

Effects of Combined Physical and Cognitive Exercises on Cognition and Mobility in Patients With Mild Cognitive Impairment: A Randomized Clinical Trial

ImportanceAlthough participation in physical and cognitive activities is encouraged to reduce the risk of dementia, the preventive efficacy of these activities for patients with mild cognitive impairment is unestablished. ObjectiveTo compare the cognitive and mobility effects of a 40-week program of combined cognitive and physical activity with those of a health education program. DesignA randomized, parallel, single-blind controlled trial. SettingA population-based study of participants recruited from Obu, a residential suburb of Nagoya, Japan. ParticipantsBetween August 2011 and February 2012, we evaluated 945 adults 65 years or older with mild cognitive impairment, enrolled 308, and randomly assigned them to the combined activity group (n = 154) or the health education control group (n = 154). InterventionsThe combined activity program involved weekly 90-minute sessions for 40 weeks focused on physical and cognitive activities. The control group attended 90-minute health promotion classes thrice during the 40-week trial period. MeasurementThe outcome measures were assessed at the study's beginning and end by personnel blinded to mild cognitive impairment subtype and group. The primary endpoints were postintervention changes in scores on (1) the Mini-Mental State Examination as a measure of general cognitive status and memory, (2) the Wechsler Memory Scale-Revised–Logical Memory II, and (3) the Rey Auditory Verbal Learning Test. We applied mobility assessments and assessed brain atrophy with magnetic resonance imaging. ResultsCompared with the control group, the combined activity group showed significantly greater scores on the Mini-Mental State Examination (difference = 0.8 points, P = .012) and Wechsler Memory Scale-Revised–Logical Memory II (difference = 1.0, P = .004), significant improvements in mobility and the nonmemory domains and reduced left medial temporal lobe atrophy in amnestic mild cognitive impairment (Z-score difference = −31.3, P < .05). ConclusionCombined physical and cognitive activity improves or maintains cognitive and physical performance in older adults with mild cognitive impairment, especially the amnestic type.

What can DTI tell about early cognitive impairment? – Differentiation between MCI subtypes and healthy controls by diffusion tensor imaging

Mild cognitive impairment (MCI) gained a lot of interest recently, especially that the conversion rate to Alzheimer Disease (AD) in the amnestic subtype (aMCI) is higher than in the non-amnestic subtype (naMCI). We aimed to determine whether and how diffusion-weighted MRI (DWI) using the diffusion tensor model (DTI) can differentiate MCI subtypes from healthy subjects. High resolution 3D T1W and DWI images of patients (aMCI, n = 18; naMCI, n = 20; according to Petersen criteria) and controls (n = 27) were acquired at 3T and processed using ExploreDTI and SPM. Voxel-wise and region of interest (ROI) analyses of fractional anisotropy (FA) and mean diffusivity (MD) were performed with ANCOVA; MD was higher in aMCI compared to controls or naMCI in several grey and white matter (GM, WM) regions (especially in the temporal pole and the inferior temporal lobes), while FA was lower in WM ROI-s (e.g. left Cingulum). Moreover, significant correlations were identified between verbal fluency, visual and verbal memory performance and DTI metrics. Logistic regression showed that measuring FA of the crus of fornix along GM volumetry improves the discrimination of aMCI from naMCI. Additional information from DWI/DTI aids preclinical detection of AD and may help detecting early non-Alzheimer type dementia, too.

The Relationships Between Components of Metabolic Syndrome and Mild Cognitive Impairment Subtypes: A Cross-Sectional Study of Japanese Older Adults.

The associations between components of metabolic syndrome (MetS) and mild cognitive impairment (MCI) subtypes remain unclear. The study aim was to identify the prevalence of MetS for MCI subtypes and to investigate sex differences in the association between MetS and MCI subtypes in older Japanese adults. The study analyzed data from 3,312 men and women aged 70 years or more. MetS was diagnosed according to International Diabetes Federation criteria. Participants completed cognitive tests and were categorized into normal cognition, amnestic MCI (aMCI), and non-amnestic MCI (naMCI). The associations between MetS and its components and MCI subtypes were analyzed using multiple logistic regression. MetS prevalence was greater in participants with naMCI (men: p = 0.030; women: p = 0.040). Participants with naMCI showed higher odds ratios (OR) of MetS (men: 2.45, 95% confidence intervals (CI): 1.13-5.32; women: OR: 1.94, 95% CI: 1.12-3.39) compared with participants with normal cognition. MetS was not associated with aMCI. Analysis of MetS components showed that raised glucose (OR: 1.62, 95% CI: 1.19-2.22) and reduced high-density lipoprotein cholesterol (OR: 1.97, 95% CI: 1.25-3.12) were associated with naMCI in men. In women, raised blood pressure (OR: 1.42, 95% CI: 1.03-1.94) and raised glucose (OR: 1.32, 95% CI: 1.02-1.71) were associated with naMCI. MetS was associated only with naMCI regardless of sex, which suggests etiologic differences in MCI subtypes. We also found sex differences in the relationship between naMCI risk and MetS and its components.

Comparison of Error Types and Qualitative Analysis of Correct Responses in a Confrontation Naming Test for Subtypes of Mild Cognitive Impairment

ë°°ê²½ 및 ëª©ì  ê²½ë„ì¸ì§€ìž¥ì• (mild cognitive impairment, MCI) 환자는 인지기능의 손상 양상이 다양한 ì´ì§ˆì ì¸ 집단이므로, MCI í•˜ìœ„ìœ í˜•ì˜ 특징을 살펴보는 것이 중요하다. 본 연구는 단일영역 기억상실형 ê²½ë„ì¸ì§€ìž¥ì• (amnestic single-domain MCI, asMCI), 다영역 기억상실형 ê²½ë„ì¸ì§€ìž¥ì• (amnestic multiple-domain MCI, amMCI), 비기억상실형 ê²½ë„ì¸ì§€ìž¥ì• (non-aMCI)의 세 MCI 하위집단과 ì¼ë°˜ë ¸ì¸ì—ê²Œ 대면이름대기 ê³¼ì œë¥¼ 실시하여 ê·¸ 특성을 살펴보았다. 방법 대상자는 MCI 환자 96ëª (asMCI 27ëª , amMCI 39ëª , non-aMCI 30ëª )ê³¼ ì¼ë°˜ë ¸ì¸ 30ëª ì´ì—ˆë‹¤. 한국판 보스톤 이름대기 ê³¼ì œ 단축형인 K-BNT-15를 실시하여, 집단 간 ê³¼ì œì˜ ì´ì , ì˜¤ë¥˜ìœ í˜•(시지각, 의미, 음운, 비연관, 기타)의 비율, ì •ë°˜ì‘ 중 ìžê°€ìˆ˜ì •ê³¼ 시간지연반응의 비율을 비교하였다. ê²°ê³¼ 첫째, ì´ì ì€ amMCI와 asMCI가 ì¼ë°˜ë ¸ì¸ê³¼ non-aMCI보다 ìœ ì˜í•˜ê²Œ 낮았다. 둘째, ì˜¤ë¥˜ìœ í˜• 중 의미 오류만 집단 간 차이를 보였다. ì ‹ì§¸, ìžê°€ìˆ˜ì •ê³¼ 시간지연반응 비율은 MCI 하위집단이 ì¼ë°˜ë ¸ì¸ë³´ë‹¤ 높았다. 특히, ìžê°€ìˆ˜ì •ë°˜ì‘ 비율은 ê¸°ì–µë ¥ 외의 다른 인지기능 ì €í•˜ê°€ 있는 MCI 집단에서, 시간지연반응은 ê¸°ì–µë ¥ 손상이 있는 MCI 집단에서 더 높았다. ë ¼ì˜ 및 ê²°ë¡ MCI í•˜ìœ„ìœ í˜•ì€ 이름대기 ëŠ¥ë ¥ 손상 양상에 차이가 있으며, 이는 의미기억, 어휘-ì˜ë¯¸ë¡ ì  ì²˜ë¦¬ê³¼ì • 및 집행기능과 같은 다른 ì¸ì§€ëŠ¥ë ¥ 손상과 관계된다. 따라서 대면이름대기 ê³¼ì œì—ì„œ ì˜¤ë¥˜ìœ í˜•ê³¼ ì •ë°˜ì‘ì˜ ì§ˆì  분석은 MCI의 í•˜ìœ„ìœ í˜•ì„ 확인하는 데 ìœ ìš©í• ìˆ˜ 있다. Keywords: ê²½ë„ì¸ì§€ìž¥ì• , 이름대기, ì˜¤ë¥˜ìœ í˜•, ìžê°€ìˆ˜ì •, 시간지연

Neurocognitive and Behavioral Indexes for Identifying the Amnestic Subtypes of Mild Cognitive Impairment.

Early identification of amnestic mild cognitive impairment (aMCI) subtypes is important for early diagnosis and prognosis of Alzheimer’s disease. Healthy, single-domain (sdaMCI) and multiple-domain aMCI (mdaMCI) participants performed an auditory-visual distraction-attention task. Event-related brain potentials (ERPs) were recorded while the participants performed the task to evaluate Go/NoGo N2 and P3 ERP components. The results showed the expected behavioral and cognitive decline in mdaMCI participants relative to controls (fewer hits, longer reaction times [RTs], slightly smaller Go-N2 and NoGo-N2 amplitudes), while sdaMCI participants showed some decline (slightly longer RTs, smaller Go- and NoGo-N2 amplitudes) along with some unexpected results (a late positive slow wave, PSW) and good levels of execution. In addition, some of these parameters proved to be useful markers. Thus, the number of hits was the best marker for diagnosing mdaMCI participants (distinguishing them from controls, from sdaMCI participants, and from both groups together), while the PSW amplitude was the best marker for diagnosing sdaMCI participants (distinguishing them from controls, and from control & mdaMCI participants).

A computerized test for the assessment of mild cognitive impairment subtypes in sentence processing

ABSTRACTThis study examines thesentence processing ability of mild cognitive impairment (MCI) subtypes. In addition to standard MCI neuropsychological tests, an experimental approach was applied to assess language. 133 people (93 MCI/40 controls) participated in novel computerized sentence processing tasks. Results presented statistically significant differences between MCI/controls andMCI subtypes (ANOVA):(a) duration F(2,92) = 19.259,p < .001) in sentence construction; (b) correct answers (F(2, 89) = 8.560,p < .001) and duration (F2,89) = 15.525,p < .001)in text comprehension; (c) correct answers (F(2, 92) = 8.975,p < .001) andduration (F(2, 92) = 4.360,p = .016) in metaphoric sentences comprehension; (d) correct answers (F(2, 92) = 12.836,p < .001) andduration (F(2, 92) = 10.974,p < .001) in verb form generation. Subtle changes in MCIsubtypes could affect sentence processing and provide useful information for cognitive decline risk estimation and screening purposes.

Self-Awareness for Memory Impairment in Amnestic Mild Cognitive Impairment: A Longitudinal Study.

To assess memory impairment insight as a predictor of dementia and Alzheimer's disease (AD) in amnestic mild cognitive impairment (MCI). To verify whether the awareness of memory impairment assessed by Geriatric Depression Scale (GDS) was associated with the risk of progression to dementia and AD in a cohort of MCI, we used a Cox regression model adjusted for age, sex, education, subtypes of amnestic MCI, Mini-Mental State Examination, Cumulative Illness Rating Scale severity index, and apolipoprotein E genotype. During a follow-up of 27.7 (20.8) months, 205 (63.3%) of 324 patients with amnestic MCI progressed to dementia, including 141 to AD. No association was found in the unadjusted, partially adjusted (for sociodemographic variables), and fully adjusted multivariate Cox analysis between the awareness of memory impairment and the progression to dementia and AD. Awareness or anosognosia of memory deficits, identified by GDS, is not useful to predict progression to dementia of patients with amnestic MCI.

Differentiating between subtypes of primary progressive aphasia and mild cognitive impairment on a modified version of the Frontal Behavioral Inventory.

Behavioral assessment has been investigated in frontotemporal lobar degeneration and Alzheimer’s disease, but has not been explored extensively in subtypes of primary progressive aphasia (PPA). We explored the ability of a modified version of the Frontal Behavioral Inventory (FBI-mod) to discriminate between patients with distinct subtypes of PPA and patients with mild cognitive impairment (MCI). We hypothesized that individuals with nonfluent agrammatic PPA (nfaPPA) would have higher negative behavior scores than other groups and that individuals with semantic variant PPA (svPPA) would have higher disinhibition scores than other groups. Family members and/or caregivers of 120 individuals with PPA and MCI (mean age 69.54+8.75 years; 65 (54%) female; education 16.06±2.68 years; disease duration 46.47±34.26 months) completed the FBI-mod [logopenic PPA (lvPPA) n = 40. nfaPPA n = 29, svPPA n = 27, MCI n = 24]. The groups were not significantly different in age, gender, education, or disease duration. There were no significant differences between the groups for negative behaviors (p = 0.72) and disinhibition scores (p = 0.14). When comparing negative and disinhibition scores (in percent), negative scores were significantly higher in all groups (p < 0.001). When comparing subtest items, there was a pairwise difference between lvPPA and svPPA for restlessness (lvPPA < svPPA, p = 0.02, after adjusting for multiple between-group comparisons). There was a significant difference in the proportion of severe neglect between the groups with lvPPA having a lower proportion than the other two variants (p = 0.05), and there was a significant difference in the proportion of severe poor judgment between the groups with lvPPA also having a lower proportion than nfaPPA (p = 0.04). This study reveals the greater negative behavioral disturbance than disinhibition in the PPA and MCI groups of similar age and duration since onset and identifies different profiles for some specific behaviors for the PPA groups. These findings may have clinical and practical implications.

Biomarkers in subtypes of mild cognitive impairment and subjective cognitive decline.

ObjectivesPreclinical Alzheimers disease (AD) patients may or may not show cognitive impairment on testing. AD biomarkers are central to the identification of those at low, intermediate, or high risk of later dementia due to AD. We investigated biomarker distribution in those identified as subjective cognitive decline (SCD), amnestic (aMCI), and nonamnestic (naMCI) mild cognitive impairment (MCI) subtypes. In addition, the clinical groups were compared with controls on downstream neuroimaging markers.Materials and MethodsCerebrospinal fluid (CSF) amyloid‐β42 (A β42) and total tau (t‐tau), phosphorylated tau (p‐tau), fluorodeoxyglucose (FDG), positron‐emission tomography (PET), and MRI neuroimaging measures were collected from 116 memory clinic patients. They were characterized as SCD, aMCI, and naMCI according to comprehensive neuropsychological criteria. ANOVAs were used to assess differences when biomarkers were treated as continuous variables and chi square analyses were used to assess group differences in distribution of biomarkers.ResultsWe did not find any between group differences in Aβ42, nor in p‐tau, but we observed elevated t‐tau in aMCI and SCD relative to the naMCI group. Significantly lower cortical glucose metabolism (as measured by FDG PET) was found in aMCI relative to SCD and controls, and there was a trend for lower metabolism in naMCI. Significant thinner entorhinal cortex (ERC) was found in aMCI and SCD. As expected biomarkers were significantly more frequently pathological in aMCI than in naMCI and SCD, whereas the naMCI and SCD groups displayed similar pathological biomarker burden.Conclusions aMCI cases show the most pathologic biomarker burden. Interestingly naMCI and SCD subjects show similar levels of pathological biomarkers albeit the former displayed neuropsychological deficits. That the latter group may represent a risk group is supported by our observation of both elevated CSF tau and thinner ERC relative to controls.

Imaging and neuropsychological correlates of white matter lesions in different subtypes of Mild Cognitive Impairment: A systematic review.

White matter lesions (WML) are prevalent in older adults. The association between WML and cognition in different subtypes of Mild Cognitive Impairment (MCI) is inconsistent in the literature. We aim to provide a systematic review on the impact of WML in different subtypes of MCI, and discuss the recent findings on white matter plasticity. We reviewed peer-reviewed articles from January 2011 to August 2016 and identified 12 studies investigating the association between WML and subtypes of MCI with both neuroimaging and cognitive measures. Our review shows that 1) WM abnormality was identified between different subtypes of MCI and healthy controls on diffusion imaging; 2) neither visual ratings of WML nor its volumetry differentiate different subtypes of MCI or its prognosis to dementia; and 3) cognitive correlates of WML were evident in the Amnestic-type MCI in the domains of memory, language, psychomotor speed, attention and executive functions. Cognitive reserve and the plasticity of white matter may modulate the impact of WML on the manifestation of the neurodegenerative disease. Further research is needed to study the plasticity of white matter in the MCI population to evaluate its potential clinical application.

Statistically Derived Subtypes and Associations with Cerebrospinal Fluid and Genetic Biomarkers in Mild Cognitive Impairment: A Latent Profile Analysis

Research demonstrates heterogeneous neuropsychological profiles among individuals with mild cognitive impairment (MCI). However, few studies have included visuoconstructional ability or used latent mixture modeling to statistically identify MCI subtypes. Therefore, we examined whether unique neuropsychological MCI profiles could be ascertained using latent profile analysis (LPA), and subsequently investigated cerebrospinal fluid (CSF) biomarkers, genotype, and longitudinal clinical outcomes between the empirically derived classes. A total of 806 participants diagnosed by means of the Alzheimer's Disease Neuroimaging Initiative (ADNI) MCI criteria received a comprehensive neuropsychological battery assessing visuoconstructional ability, language, attention/executive function, and episodic memory. Test scores were adjusted for demographic characteristics using standardized regression coefficients based on "robust" normal control performance (n=260). Calculated Z-scores were subsequently used in the LPA, and CSF-derived biomarkers, genotype, and longitudinal clinical outcome were evaluated between the LPA-derived MCI classes. Statistical fit indices suggested a 3-class model was the optimal LPA solution. The three-class LPA consisted of a mixed impairment MCI class (n=106), an amnestic MCI class (n=455), and an LPA-derived normal class (n=245). Additionally, the amnestic and mixed classes were more likely to be apolipoprotein e4+ and have worse Alzheimer's disease CSF biomarkers than LPA-derived normal subjects. Our study supports significant heterogeneity in MCI neuropsychological profiles using LPA and extends prior work (Edmonds et al., 2015) by demonstrating a lower rate of progression in the approximately one-third of ADNI MCI individuals who may represent "false-positive" diagnoses. Our results underscore the importance of using sensitive, actuarial methods for diagnosing MCI, as current diagnostic methods may be over-inclusive. (JINS, 2017, 23, 564-576).

Prognostic Accuracy of Mild Cognitive Impairment Subtypes at Different Cut-Off Levels

Background/Aims: The prognostic accuracy of mild cognitive impairment (MCI) in clinical settings is debated, variable across criteria, cut-offs, subtypes, and follow-up time. We aimed to estimate the prognostic accuracy of MCI and the MCI subtypes for dementia using three different cut-off levels. Methods: Memory clinic patients were followed for 2 (n = 317, age 63.7 ± 7.8) and 4-6 (n = 168, age 62.6 ± 7.4) years. We used 2.0, 1.5, and 1.0 standard deviations (SD) below the mean of normal controls (n = 120, age 64.1 ± 6.6) to categorize MCI and the MCI subtypes. Prognostic accuracy for dementia syndrome at follow-up was estimated. Results: Amnestic multi-domain MCI (aMCI-md) significantly predicted dementia under all conditions, most markedly when speed/attention, language, or executive function was impaired alongside memory. For aMCI-md, sensitivity increased and specificity decreased when the cut-off was lowered from 2.0 to 1.5 and 1.0 SD. Non-subtyped MCI had a high sensitivity and a low specificity. Conclusion: Our results suggest that aMCI-md is the only viable subtype for predicting dementia for both follow-up times. Lowering the cut-off decreases the positive predictive value and increases the negative predictive value of aMCI-md. The results are important for understanding the clinical prognostic utility of MCI, and MCI as a non-progressive disorder.

Definición y prevalencia del deterioro cognitivo leve

Cognition is the ability that allows humans to carry out their lives without difficulty, resolving problems and situations, and to continue to learn and correctly process information from the environment for its subsequent retrieval and use. In persons with normal or physiological brain ageing, this ability is maintained throughout their lives. However, individuals with abnormal or pathological ageing could be affected by distinct degrees of impairment of higher brain functions. The term mild cognitive impairment (MCI) entered the lexicon in 1988 to describe a syndrome encompassing greater than expected cognitive impairment for the person’s age and cultural environment. At that time, MCI was considered a degenerative process that preceded dementia. In the last 30 years, it has become clear that not all patients with MCI will progress to dementia. Therefore, the concept and definition of this syndrome have been constantly updated, and distinct subtypes of MCI have been established according to the affected cognitive domain. There is a need to define MCI more clearly and identify its subtypes in order to establish its impact on an ageing society, identify persons at risk of progressing to dementia, and implement early intervention strategies aimed at improving the mental health of the elderly population.

Heterogeneity of Neuropsychological Impairment in HIV Infection: Contributions from Mild Cognitive Impairment.

Despite longstanding acknowledgement of the heterogeneity of HIV-associated neurocognitive disorders (HAND), existing HAND diagnostic methods classify according to the degree of impairment, without regard to the pattern of neuropsychological strengths and weaknesses. Research in mild cognitive impairment (MCI) has demonstrated that classifying individuals into subtypes by both their level and pattern of impairment, using either conventional or statistical methods, has etiologic and prognostic utility. Methods for characterizing the heterogeneity of MCI provide a framework that can be applied to other disorders and may be useful in clarifying some of the current challenges in the study of HAND. A small number of studies have applied these methods to examine the heterogeneity of neurocognitive function among individuals with HIV. Most have supported the existence of multiple subtypes of neurocognitive impairment, with some evidence for distinct clinicodemographic features of these subtypes, but a number of gaps exist. Following a review of diagnostic methods and challenges in the study of HAND, we summarize the literature regarding conventional and empirical subtypes of MCI and HAND and identify directions for future research regarding neurocognitive heterogeneity in HIV infection.