Multi-domain Amnestic Mild Cognitive Impairment Research Articles

Neuroimaging-guided diagnosis of possible FTLD-FUS pathology: a case report

BackgroundThis case report presents a patient with progressive memory loss and choreiform movements.Case presentationNeuropsychological tests indicated multi-domain amnestic mild cognitive impairment (aMCI), and neurological examination revealed asymmetrical involuntary hyperkinetic movements. Imaging studies showed severe left-sided atrophy and hypometabolism in the left frontal and temporoparietal cortex. [18F]Flortaucipir PET exhibited moderately increased tracer uptake in hypometabolic areas. The diagnosis initially considered Alzheimer’s disease (AD), frontotemporal degeneration (FTD), and corticobasal degeneration (CBD), cerebral hemiatrophy syndrome, but imaging and cerebrospinal fluid analysis excluded AD and suggested fused-in-sarcoma-associated FTD (FTLD-FUS), a subtype of the behavioural variant of FTD.ConclusionsOur case highlights that despite the lack of specific FUS biomarkers the combination of clinical features and neuroimaging biomarkers can guide choosing the most likely differential diagnosis in a complex neurological case. Imaging in particular allowed an accurate measure of the topography and severity of neurodegeneration and the exclusion of AD-related pathology.

Face-to-face vs. Telerehabilitation language and cognitive training in patients with multi-domain amnestic mild cognitive impairment

The recent coronavirus emergency raised the question of whether telerehabilitation could be as effective as conventional face-to-face intervention. The aim of the present study was to compared language and cognitive training delivered to patients from a distance, through telecommunication systems, for the same intervention conducted on a face-to-face mode in patients with multi domain amnestic MCI (md-aMCI). To this end, 30 patients diagnosed with md-aMCI took part in the present study. The participants divided into two groups; one group received conventional face-to-face training and the other group received Telerehabilitation training. Both groups received language training using paper and pencil tasks and cognitive training using the Rehacom software. The training lasted 15 weeks and was delivered twice a week, for 60 minutes per session. The conventional face-to-face mode had a significant impact on cognitive (delayed and working memory, processing speed, executive function, and attention) and language domains (naming, word recognition, and semantic fluency). The telerehabilitation method had a beneficial impact on delayed memory, naming, and semantic fluency. The results of our study provide evidence that both telerehabilitation and face-to-face language and cognitive training seem to have a positive impact in patients with md-aMCI, with face-to-face training improving more domains than telerehabilitation.

Exploring the impact of intensified multiple session tDCS over the left DLPFC on brain function in MCI: a randomized control trial

Transcranial direct current stimulation combined with cognitive training (tDCS-cog) represents a promising approach to combat cognitive decline among healthy older adults and patients with mild cognitive impairment (MCI). In this 5-day-long double-blinded randomized trial, we investigated the impact of intensified tDCS-cog protocol involving two trains of stimulation per day on working memory (WM) enhancement in 35 amnestic and multidomain amnestic MCI patients. Specifically, we focused to improve WM tasks relying on top-down attentional control and hypothesized that intensified tDCS would enhance performance of visual object matching task (VOMT) immediately after the stimulation regimen and at a 1-month follow-up. Secondarily, we explored whether the stimulation would augment online visual working memory training. Using fMRI, we aimed to elucidate the neural mechanisms underlying the intervention effects by analyzing BOLD activations during VOMT. Our main finding revealed no superior after-effects of tDCS-cog over the sham on VOMT among individuals with MCI as indicated by insignificant immediate and long-lasting after-effects. Additionally, the tDCS-cog did not enhance online training as predicted. The fMRI analysis revealed brain activity alterations in right insula that may be linked to tDCS-cog intervention. In the study we discuss the insignificant behavioral results in the context of the current evidence in tDCS parameter space and opening the discussion of possible interference between trained cognitive tasks.

Associations between air pollution exposure and empirically derived subtypes of mild cognitive impairment in older women

AbstractBackgroundExposure to air pollution in older adulthood is a novel risk factor for mild cognitive impairment (MCI). MCI is a heterogenous construct with different subtypes likely reflecting different disease etiologies. Understanding if long‐term exposure to air pollution is differentially associated with MCI subtypes may provide insight into the neurotoxic effects of air pollution exposure on the aging brain.MethodParticipants included women from the Women’s Health Initiative Memory Study. Data from 651 women without dementia who screened positive for cognitive impairment on the modified mini‐mental state examination (3MS) and a randomly selected comparison sample of 2,560 women who were cognitively intact based on the 3MS were utilized. Participants were administered the 3MS annually (1996‐2008). Those who screened positive for cognitive impairment on the 3MS completed the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) cognitive battery and the Trailmaking Test parts A and B. Average annual levels of particulate matter of aerodynamic diameter<2.5 (PM2.5) and nitrogen dioxide (NO2) were estimated at the participant’s residence using regionalized national universal kriging models and averaged over the 3‐year period before the cognitive assessment. Latent class structural equation models (SEM) were constructed to identify MCI subtypes. We then examined associations between air pollution exposure and latent class membership using multinomial regression while adjusting for demographic, lifestyle, and clinical confounders.ResultFour significant MCI subtypes were identified (Figure 1): multidomain MCI (n = 147; 23%), amnestic MCI (n = 141; 22%), dysnomic/dysexecutive MCI (n = 200; 31%), and subtle MCI (n = 163; 25%). Women living in locations with higher levels of PM2.5 (per interquartile range [IQR] = 3.93 µg/m3; OR = 1.28; p = .04) or NO2 (per IQR = 9.25 ppb; OR = 1.36; p = .02) were more likely to be classified as having subtle MCI compared to normal comparisons. One IQR increase in NO2 was also associated with increased likelihood of being classified with dysnomic/dysexecutive MCI (OR = 1.38; p = .003) compared to normal comparisons.ConclusionOur study illustrates that long‐term exposure to PM2.5 and NO2 may be associated with specific subtypes of MCI. Our findings provide further evidence that air pollution may exert neurotoxic effects on brain areas underlying executive function and language ability in older women.

Enhancing cognitive control in amnestic mild cognitive impairment via at-home non-invasive neuromodulation in a randomized trial

Individuals with multi-domain amnestic mild cognitive impairment (md-aMCI) have an elevated risk of dementia and need interventions that may retain or remediate cognitive function. In a feasibility pilot study, 30 older adults aged 60–80 years with md-aMCI were randomized to 8 sessions of transcranial alternating current stimulation (tACS) with simultaneous cognitive control training (CCT). The intervention took place within the participant’s home without direct researcher assistance. Half of the participants received prefrontal theta tACS during CCT and the other half received control tACS. We observed high tolerability and adherence for at-home tACS + CCT. Within 1-week, only those who received theta tACS exhibited improved attentional abilities. Neuromodulation is feasible for in-home settings, which can be conducted by the patient, thereby enabling treatment in difficult to reach populations. TACS with CCT may facilitate cognitive control abilities in md-aMCI, but research in a larger population is needed to validate efficacy.

Adequate dietary magnesium intake may protect females but not males older than 55 years from cognitive impairment

ABSTRACT Background Magnesium is an essential nutrient required to maintain brain health throughout life, and adequate magnesium intake is positively associated with cognitive performance in older adults. However, sex differences in magnesium metabolism have not been adequately assessed in humans. Objectives We investigated sex differences in the effect of dietary magnesium intake and the risk of different types of cognitive impairment in older Chinese adults. Methods We collected and assessed dietary data and cognitive function status in people aged 55 years and older in northern China who participated in the Community Cohort Study of Nervous System Diseases from 2018 to 2019 to explore the relationship between dietary magnesium intake and the risk of each type of mild cognitive impairment (MCI) in sex-specific cohorts of older adults. Results The study included 612 people: 260 (42.5%) men and 352 (57.5%) women. Logistic regression results showed that for the total sample and women's sample, high dietary magnesium intake reduced the risk of amnestic MCI (ORtotal = 0.300; ORwomen = 0.190) and multidomain amnestic MCI (ORtotal = 0.225; ORwomen = 0.145). The results of restricted cubic spline analysis showed that the risk of amnestic MCI (ptotal = 0.0193; pwomen = 0.0351) and multidomain amnestic MCI (ptotal = 0.0089; pwomen = 0.0096) in the total sample and women's sample gradually decreased with increasing dietary magnesium intake. Conclusions The results suggest that adequate magnesium intake may have a preventive effect against the risk of MCI in older women.

The impact of mild cognitive impairment on decision-making under explicit risk conditions: Evidence from the Personality and Total Health (PATH) Through Life longitudinal study.

Previous research has indicated that cognition and executive function are associated with decision-making, however the impact of mild cognitive impairment (MCI) on decision-making under explicit risk conditions is unclear. This cross-sectional study examined the impact of MCI, and MCI subtypes, on decision-making on the Game of Dice Task (GDT), among a cohort of older adults. Data from 245 older adult participants (aged 72-78 years) from the fourth assessment of the Personality and Total Health Through Life study were analyzed. A diagnostic algorithm identified 103 participants with MCI, with subtypes of single-domain amnestic MCI (aMCI-single; n = 38), multi-domain amnestic MCI (aMCI-multi; n = 31), and non-amnestic MCI (n = 33), who were compared with an age-, sex-, education-, and income-matched sample of 142 cognitively unimpaired older adults. Decision-making scores on the GDT (net score, single number choices, and strategy changes) were compared between groups using nonparametric tests. Participants with MCI showed impaired performance on the GDT, with higher frequencies of single number choices and strategy changes. Analyses comparing MCI subtypes indicated that the aMCI-multi subtype showed increased frequency of single number choices compared to cognitively unimpaired participants. Across the sample of participants, decision-making scores were associated with measures of executive function (cognitive flexibility and set shifting). MCI is associated with impaired decision-making performance under explicit risk conditions. Participants with impairments in multiple domains of cognition showed the clearest impairments. The GDT may have utility in discriminating between MCI subtypes.

Correlates of Conversion from Mild Cognitive Impairment to Dementia with Lewy Bodies: Data from the National Alzheimer's Coordinating Center.

Many patients with dementia with Lewy bodies (DLB) miss out on the best standards of care and psychosocial support due to diagnostic delays or inaccuracies following symptom onset. This study seeks to identify baseline characteristics in individuals with mild cognitive impairment (MCI) that correlate with eventual conversion to DLB or Alzheimer's disease (AD). Baseline neuropsychological and neuropsychiatric data were analyzed in National Alzheimer's Coordinating Center participants who completed the Uniform Data Set between 2006 and 2020 and subsequently converted from MCI to DLB or AD (n = 1632). Only 6% of participants with MCI converted to DLB. Among those who converted to DLB, multidomain amnestic MCI (aMCI) was the most common subtype at study entry. As part of logistic regression analyses, odds ratios (ORs) were estimated for conversion to DLB versus AD based on study-entry characteristics, adjusting for age, sex, education, and years to diagnosis. The strongest predictors of conversion to DLB (p≤0.0001) were nonamnestic MCI versus aMCI (OR 8.2, CI [5.0, 14]), multidomain MCI versus single-domain MCI (OR 2.7, CI [1.7. 4.2]), male sex (OR 4.2, CI [2.5, 7.1]), and presence of nighttime behaviors (OR 4.4 CI [2.8, 6.9]). A diagnosis of prodromal DLB should be considered in individuals with MCI who present with prominent executive/visuospatial deficits, neuropsychiatric symptoms, and less memory impairment. Early diagnosis of DLB may guide treatment planning, including the avoidance of antipsychotic medications in patients who develop psychotic symptoms, caregiver support, and initiation of early treatment(s) once medications become available.

Fronto-temporal functional disconnection precedes hippocampal atrophy in clinically confirmed multi-domain amnestic Mild Cognitive Impairment.

Mild Cognitive Impairment (MCI) is fraught with high false positive diagnostic errors. The high rate of false positive diagnosis hampers attempts to identify reliable and valid biomarkers for MCI. Recent research suggests that aberrant functional neurocircuitries emerge prior to significant cognitive deficits. The aim of the present study was to examine this in clinically confirmed multi-domain amnestic-MCI (mdaMCI) using an established, multi-time point, methodology for minimizing false positive diagnosis. Structural and resting-state functional MRI data were acquired in healthy controls (HC, n=24), clinically-confirmed multi-domain amnestic-MCI (mdaMCI, n=14) and mild Alzheimer's Dementia (mAD, n=6). Group differences in cortical thickness, hippocampal volume and functional connectivity were investigated. Hippocampal subvolumes differentiated mAD from HC and mdaMCI. Functional decoupling of fronto-temporal networks implicated in memory and executive function differentiated HC and mdaMCI. Decreased functional connectivity in these networks was associated with poorer cognitive performance scores. Preliminary findings suggest the large-scale decoupling of fronto-temporal networks associated with cognitive decline precedes measurable structural neurodegeneration in clinically confirmed MCI and may represent a potential biomarker for disease progression.

Patterns of brain atrophy in dysexecutive amnestic mild cognitive impairment raise confidence about prodromal AD dementia

AbstractBackgroundPrediction models aimed at detecting risk of progression from Mild Cognitive Impairment (MCI) to Alzheimer’s disease (AD) dementia increase their accuracy when impaired executive functions enter the analysis. This suggests that impaired executive functions in MCI are likely linked to the prodromal stages of AD dementia. Neuroimaging assessment of such patients would allow exploring if they show AD related patterns of brain atrophy. We hypothesized that AD sensitive brain regions would show discrimination between dysexecutive amnestic MCI (maMIC) and healthy controls.MethodWe analysed 32 healthy controls and 23 MCI patients. Patients were divided in single domain amnestic MCI, multidomain amnestic MCI (i.e., with the dysexecutive component), and non‐amnestic MCI. Brain volume data entered regression models to analyse which brain regions predict group membership (control vs maMCI). Stepwise lineal regression model was then conducted to identify the brain regions with better prediction power.ResultsFour variables were able to predict group membership in simple lineal regression models: entorhinal cortex, lingual gyrus and parahippocampal gyrus in the left hemisphere and fusiform gyrus in the right hemisphere. The entorhinal cortex provided the most accurate model (F(1, 42) = 14.19, p=0.001, R2=0.24). Linear regression models were run with performance on executive function tasks including tests of switching, planning, verbal fluency and working memory. The most accurate model returned Letters and Numbers and categories fluency (F(2, 44) = 21.35, p=0.000, R2=0.48) suggesting that working memory and category generation are the functions contributing to the dysexecutive profiles observed in maMCI patients.ConclusionDysexecutive profiles in multidomain amnestic MCI together with neuroimaging volumetric analysis increase the probability of identifying the prodromal stages of AD dementia.

Application of neuropsychological criteria to classify mild cognitive impairment in the active study.

Objective: Comprehensive neuropsychological criteria (NP criteria) for mild cognitive impairment (MCI) has reduced diagnostic errors and better predicted progression to dementia than conventional MCI criteria that rely on a single impaired score and/or subjective report. This study aimed to implement an actuarial approach to classifying MCI in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study. Method: ACTIVE study participants (N = 2,755) were classified as cognitively normal (CN) or as having MCI using NP criteria. Estimated proportion of MCI participants and reversion rates were examined as well as baseline characteristics by MCI subtype. Mixed effect models examined associations of MCI subtype with 10-year trajectories of self-reported independence and difficulty performing instrumental activities of daily living (IADLs). Results: The proportion of MCI participants was estimated to be 18.8%. Of those with MCI at baseline, 19.2% reverted to CN status for all subsequent visits. At baseline, the multidomain-amnestic MCI group generally had the greatest breadth and depth of cognitive impairment and reported the most IADL difficulty. Longitudinally, MCI participants showed faster IADL decline than CN participants (multidomain-amnestic MCI > single domain-amnestic MCI > nonamnestic MCI). Conclusion: NP criteria identified a proportion of MCI and reversion rate within ACTIVE that is consistent with prior studies involving community-dwelling samples. The pattern of everyday functioning change suggests that being classified as MCI, particularly amnestic MCI, is predictive of future loss of independence. Future work will apply these classifications in ACTIVE to better understand the relationships between MCI and health, social, and cognitive intervention-related factors. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Predictive and diagnostic utility of brief neuropsychological assessment in detecting Alzheimer's pathology and progression to dementia.

Objective: To assess the role of brief neuropsychological assessments in prediction and identification of Alzheimer's disease (AD) pathology and progression to AD dementia. Method: Adults (N = 255; range = 40-81 years) with self-reported cognitive decline underwent baseline and 2-year follow-up clinical assessment, including a brief neuropsychological screening and lumbar puncture. Five different mild cognitive impairment (MCI) algorithms were applied on baseline cognitive test results: one conventional, three amnestic (lenient, stringent, multidomain), and one comprehensive criterion. We compared predictive and diagnostic accuracy of these MCI criteria by performing logistic regression analyses and calculating diagnostic accuracy measures for 2-year outcomes of (1) clinical diagnosis of AD dementia and (2) cerebrospinal fluid biomarkers in the Alzheimer's continuum. Results: The lenient amnestic MCI criterion showed the largest effect size for predicting progression to AD dementia (OR = 13.762, 99% CI = 1.969-96.194, p = .001) and AD biomarkers (OR = 4.855, 99% CI = 1.974-11.924, p < .001) after 2 years. This criterion was sensitive for progression to dementia (sensitivity = 92.0%, specificity = 54.8%, positive likelihood ratio [LR+] = 2.03, LR- = 0.15) and showed the highest overall diagnostic accuracy for AD biomarkers (sensitivity = 72.7%, specificity = 59.1%, LR+ = 1.78, negative likelihood ratio [LR-] = 0.46). The multidomain amnestic MCI criterion produced the highest specificity for dementia (sensitivity = 76.0%, specificity = 73.0%, LR+ = 2.82, LR- = 0.33) and AD biomarkers (sensitivity = 46.8% specificity = 70.9% LR+ = 1.61, LR- = 0.75). Conclusions: Defining MCI using a brief neuropsychological battery provided limited accuracy for progression to AD dementia and cerebrospinal fluid Aβ. The lenient amnestic MCI criterion identified the highest number of individuals who progressed to clinical AD or showed biomarker pathology, but this approach included a substantial number of false positives. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Predictors of rate of cognitive decline in patients with amnestic mild cognitive impairment

Objective Amnestic mild cognitive impairment (MCI) is a known risk factor for conversion to Alzheimer’s disease (AD). Although substantial research has been conducted on the general profile of amnestic MCI subjects and predictors of conversion to AD, research on predictors of rate of decline has been considerably less extensive. The present study sought to more systematically and comprehensively examine predictors of rate of cognitive decline in a longitudinal sample of individuals with MCI, including age, genetic vulnerability, baseline cognitive performance, and baseline neuropsychiatric severity. Method Participants with single or multi-domain amnestic MCI (N = 151) were assessed at baseline and for a mean of 1.32 follow-up visits (mean interval from baseline to last follow-up = 1.61 years). Results Results showed that carriers of the ApoE ε4 allele declined more quickly on all three dementia severity measures compared to non-carriers. Older individuals did not decline more rapidly in dementia severity. Participants with lower executive functions composite scores and greater memory impairment severity at baseline predicted faster decline on dementia severity measures. Contrary to hypotheses, those with lower levels of depression at baseline declined more rapidly on dementia severity measures compared to those with higher levels of depression. Conclusion Identifying potential predictors of rate of decline from amnestic MCI to AD could be clinically meaningful for prognostic purposes, understanding risk and protective factors, as well as guiding future treatments and clinical trials that could aim to target and delay progression among those patients who are vulnerable to more quickly convert to AD.

Memory and Executive Dysfunction Predict Complex Activities of Daily Living Impairment in Amnestic Multi-Domain Mild Cognitive Impairment.

Specific cognitive alterations could be one of the predictors that lead to the complex activities of daily living (CADL) impairment in mild cognitive impairment (MCI) and, hence, help to explain the continuum between MCI and dementia. We aimed to reevaluate the existing uncertainty regarding the impact of memory and executive functions on CADL in patients with MCI. Caregivers of 161 patients with amnestic multi-domain MCI and of 150 patients with incipient Alzheimer's disease as well as 100 age-, sex-, and education-matched controls, completed the Interview for Deterioration in Daily Living Activities in Dementia, a suitable instrument for the description and discrimination of CADL. In addition, all patients and controls were assessed with a neuropsychological battery to measure explicit memory and executive functions performance. Multiple regression analyses showed that in the group of patients with amnestic multi-domain MCI, 67.4% of the variability of the CADL impairment was explained by worse performance on executive functions tests (p < 0.0001) and 41.8% by different explicit memory components impairment (p < 0.0001). Further, in patients with incipient AD, 44.0% of the variability of CADL impairment was explained by worse performance on executive functions tests (p < 0.0001) and 39.9% by different explicit memory components worsening (p < 0.0001). Memory and executive functions alterations impact similarly on the CADL in both amnestic multi-domain MCI and incipient Alzheimer's disease. Given the continuum that exists between both conditions, we conclude that CADL impairment may be an important early step in the evolution towards Alzheimer's disease from amnestic multi-domain MCI.

Neurocognitive indexes of multi-domain amnestic mild cognitive impairment during an old/new words recognition task

Neurocognitive indexes of multi-domain amnestic mild cognitive impairment during an old/new words recognition task

P2‐471: CLUSTERING EXECUTIVE FUNCTIONS YIELDS MCI PROFILES THAT SIGNIFICANTLY PREDICT CONVERSION TO AD DEMENTIA

Background: It has been acknowledged that executive dysfunctions hold potential as early predictors of progression from Mild Cognitive Impairment (MCI) to Alzheimer’s disease (AD) dementia. Executive deficits have a significant impact on the ability to perform activities of daily living (ADL), and as such, can lead to the transition from MCI to AD dementia. However, the extent to which executive impairments can yield identifiable cognitive profiles which can increase the risk of MCI to AD dementia progression has not been well investigated to date. Method: We analysed 152 patients (52 healthy controls and 100 MCI) who were subsequently divided based on the traditional classification of MCI (single domain amnestic MCI, multidomain amnestic MCI and non-amnestic MCI). Eight tests, assessing executive functions were administered at baseline and at 1-year-follow-up. Screening tests of cognitive and functional abilities were also used. A new dysexecutive MCI classification was developed relying on k-means cluster analysis through which three clusters were identified. Baseline data entered simple lineal regression models to examine whether such a classification based on executive profiles could significantly predict progression to AD dementia a year later. Results: The dysexecutive classification accounted for 63% of the variance linked to MCI to AD conversion even when controlling for the severity of disease at baseline (F(1, 68) = 116.25, p=0.000, R2=0.63). Such a prediction power was not observed when the classical MCI classification based on memory profiles alone entered the model as a predictor (F(1, 68) = 5.09, p=0.955, R2=0.07). Conclusion: Considering dysexecutive profiles of MCI patients may increase the accuracy of prediction models aimed at detecting risk of progressing to AD dementia. MCI patients with worse performance on executive tests seem to hold a higher risk of conversion and such a risk seems to be accounted for neither by memory impairments nor by the severity of the disease at baseline.

Decreased Bilateral FDG-PET Uptake and Inter-Hemispheric Connectivity in Multi-Domain Amnestic Mild Cognitive Impairment Patients: A Preliminary Study.

Background: Amnestic mild cognitive impairment (aMCI) is a heterogeneous condition. Based on clinical symptoms, aMCI could be categorized into single-domain aMCI (SD-aMCI, only memory deficit) and multi-domain aMCI (MD-aMCI, one or more cognitive domain deficit). As core intrinsic functional architecture, inter-hemispheric connectivity maintains many cognitive abilities. However, few studies investigated whether SD-aMCI and MD-aMCI have different inter-hemispheric connectivity pattern.Methods: We evaluated inter-hemispheric connection pattern using fluorine-18 positron emission tomography – fluorodeoxyglucose (18F PET-FDG), resting-state functional MRI and structural T1 in 49 controls, 32 SD-aMCI, and 32 MD-aMCI patients. Specifically, we analyzed the 18F PET-FDG (intensity normalized by cerebellar vermis) in a voxel-wise manner. Then, we estimated inter-hemispheric functional and structural connectivity by calculating the voxel-mirrored homotopic connectivity (VMHC) and corpus callosum (CC) subregions volume. Further, we correlated inter-hemispheric indices with the behavioral score and pathological biomarkers.Results: We found that MD-aMCI exhibited more several inter-hemispheric connectivity damages than SD-aMCI. Specifically, MD-aMCI displayed hypometabolism in the bilateral middle temporal gyrus (MTG), inferior parietal lobe, and left precuneus (PCu) (p < 0.001, corrected). Correspondingly, MD-aMCI showed decreased VMHC in MTG, PCu, calcarine gyrus, and postcentral gyrus, as well as smaller mid-posterior CC than the SD-aMCI and controls (p < 0.05, corrected). Contrary to MD-aMCI, there were no neuroimaging indices with significant differences between SD-aMCI and controls, except reduced hypometabolism in bilateral MTG. Within aMCI patients, hypometabolism and reduced inter-hemispheric connectivity correlated with worse executive ability. Moreover, hypometabolism indices correlated to increased amyloid deposition.Conclusion: In conclusion, patients with MD-aMCI exhibited the more severe deficit in inter-hemispheric communication than SD-aMCI. This long-range connectivity deficit may contribute to cognitive profiles and potentially serve as a biomarker to estimate disease progression of aMCI patients.

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.

Unmasking the benefits of donepezil via psychometrically precise identification of mild cognitive impairment: A secondary analysis of the ADCS vitamin E and donepezil in MCI study

IntroductionCriteria for mild cognitive impairment (MCI) used in many clinical trials are susceptible to “false-positive (FP)” errors that can be avoided by an actuarial psychometric approach. MethodsCluster analysis was applied to baseline neuropsychological test data from 756 MCI participants in the Alzheimer's Disease Cooperative Study donepezil trial. Treatment groups were compared after FP MCI cases were removed. ResultsCluster analyses revealed three groups: “single-domain amnestic MCI” (31%), “multi-domain amnestic MCI” (39%), and “FP MCI” (30%). After removing FP MCI cases, the donepezil treatment group had a lower rate of progression to Alzheimer's disease and better performance on cognitive tests than the placebo/vitamin E group. DiscussionRemoval of FP MCI diagnoses unmasked beneficial effects of donepezil, despite a 30% reduction in sample size. MCI subject selection based on actuarial methods with comprehensive neuropsychological test data can result in more efficient clinical trials and improved ability to detect treatment effects.

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.